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Sample records for accelerated brain aging

  1. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels

    PubMed Central

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F.; Eszes, Marika; Faull, Richard L.M.; Curtis, Maurice A.; Waldvogel, Henry J.; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V.; Coppola, Giovanni; Yang, X. William

    2016-01-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=−0.41, p=5.5×10−8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels. PMID:27479945

  2. Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

    PubMed

    Kolosova, Nataliya G; Vitovtov, Anton O; Muraleva, Natalia A; Akulov, Andrey E; Stefanova, Natalia A; Blagosklonny, Mikhail V

    2013-06-01

    Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

  3. Accelerated brain aging in schizophrenia and beyond: a neuroanatomical marker of psychiatric disorders.

    PubMed

    Koutsouleris, Nikolaos; Davatzikos, Christos; Borgwardt, Stefan; Gaser, Christian; Bottlender, Ronald; Frodl, Thomas; Falkai, Peter; Riecher-Rössler, Anita; Möller, Hans-Jürgen; Reiser, Maximilian; Pantelis, Christos; Meisenzahl, Eva

    2014-09-01

    Structural brain abnormalities are central to schizophrenia (SZ), but it remains unknown whether they are linked to dysmaturational processes crossing diagnostic boundaries, aggravating across disease stages, and driving the neurodiagnostic signature of the illness. Therefore, we investigated whether patients with SZ (N = 141), major depression (MD; N = 104), borderline personality disorder (BPD; N = 57), and individuals in at-risk mental states for psychosis (ARMS; N = 89) deviated from the trajectory of normal brain maturation. This deviation was measured as difference between chronological and the neuroanatomical age (brain age gap estimation [BrainAGE]). Neuroanatomical age was determined by a machine learning system trained to individually estimate age from the structural magnetic resonance imagings of 800 healthy controls. Group-level analyses showed that BrainAGE was highest in SZ (+5.5 y) group, followed by MD (+4.0), BPD (+3.1), and the ARMS (+1.7) groups. Earlier disease onset in MD and BPD groups correlated with more pronounced BrainAGE, reaching effect sizes of the SZ group. Second, BrainAGE increased across at-risk, recent onset, and recurrent states of SZ. Finally, BrainAGE predicted both patient status as well as negative and disorganized symptoms. These findings suggest that an individually quantifiable "accelerated aging" effect may particularly impact on the neuroanatomical signature of SZ but may extend also to other mental disorders.

  4. Senescence-accelerated Mice (SAMs) as a Model for Brain Aging and Immunosenescence

    PubMed Central

    Shimada, Atsuyoshi; Hasegawa-Ishii, Sanae

    2011-01-01

    The Senescence-Accelerated Mouse (SAM) represents a group of inbred mouse strains developed as a model for the study of human aging and age-related diseases. Senescence-prone (SAMP) strains exhibit an early onset of age-related decline in the peripheral immunity such as thymic involution, loss of CD4+ T cells, impaired helper T cell function, decreased antibody-forming capacity, dysfunction of antigen-presenting cells, decreased natural killer activity, increased auto-antibodies, and susceptibility to virus infection. Senescence-prone SAMP10 mice undergo age-related changes in the brain such as brain atrophy, shrinkage and loss of cortical neurons, retraction of cortical neuronal dendrites, loss of dendritic spines, loss of synapses, impaired learning and memory, depressive behavior, accumulation of neuronal DNA damage, neuronal ubiquitinated inclusions, reduced hippocampal cholinergic receptors, decreased neurotrophic factors, decreased hippocampal zinc and zinc transporters, increased sphyngomyelinase, and elevated oxidative-nitrative stress. Recent data indicating increased pro-inflammatory cytokines in the brain of SAMP10 mice are directing investigators toward an integration of immune and neural abnormalities to enhance understanding of the principles of brain aging. We highlight how mouse brain cells adopt cytokine-mediated responses and how SAMP10 mice are defective in these responses. SAMP10 model would be useful to study how age-related disturbances in peripheral immunity have an impact on dysregulation of brain tissue homeostasis, resulting in age-related neurodegeneration. PMID:22396891

  5. Accelerated epigenetic aging in brain is associated with pre-mortem HIV-associated neurocognitive disorders.

    PubMed

    Levine, Andrew J; Quach, Austin; Moore, David J; Achim, Cristian L; Soontornniyomkij, Virawudh; Masliah, Eliezer; Singer, Elyse J; Gelman, Benjamin; Nemanim, Natasha; Horvath, Steve

    2016-06-01

    HIV infection leads to age-related conditions in relatively young persons. HIV-associated neurocognitive disorders (HAND) are considered among the most prevalent of these conditions. To study the mechanisms underlying this disorder, researchers need an accurate method for measuring biological aging. Here, we apply a recently developed measure of biological aging, based on DNA methylation, to the study of biological aging in HIV+ brains. Retrospective analysis of tissue bank specimens and pre-mortem data was carried out. Fifty-eight HIV+ adults underwent a medical and neurocognitive evaluation within 1 year of death. DNA was obtained from occipital cortex and analyzed with the Illumina Infinium Human Methylation 450K platform. Biological age determined via the epigenetic clock was contrasted with chronological age to obtain a measure of age acceleration, which was then compared between those with HAND and neurocognitively normal individuals. The HAND and neurocognitively normal groups did not differ with regard to demographic, histologic, neuropathologic, or virologic variables. HAND was associated with accelerated aging relative to neurocognitively normal individuals, with average relative acceleration of 3.5 years. Age acceleration did not correlate with pre-mortem neurocognitive functioning or HAND severity. This is the first study to demonstrate that the epigenetic age of occipital cortex samples is associated with HAND status in HIV+ individuals pre-mortem. While these results suggest that the increased risk of a neurocognitive disorder due to HIV might be mediated by an epigenetic aging mechanism, future studies will be needed to validate the findings and dissect causal relationships and downstream effects.

  6. Excessive daytime sleepiness and fatigue may indicate accelerated brain aging in cognitively normal late middle-aged and older adults.

    PubMed

    Carvalho, Diego Z; St Louis, Erik K; Boeve, Bradley F; Mielke, Michelle M; Przybelski, Scott A; Knopman, David S; Machulda, Mary M; Roberts, Rosebud O; Geda, Yonas E; Petersen, Ronald C; Jack, Clifford R; Vemuri, Prashanthi

    2017-04-01

    Excessive daytime sleepiness (EDS) and fatigue increases with age. The aim of this study was to investigate the association between EDS and fatigue with cortical thickness and hippocampal volume in cognitively normal, late middle-aged and older adults. We performed a cross-sectional observational study of 1374 cognitively-normal subjects aged 50 years and older who had a structural MRI. Regional cortical thickness and hippocampal volume were measured. Multiple linear regression models were fit to explore associations between EDS and fatigue and structural MRI measures in different brain regions, adjusting for multiple covariates. EDS was defined as Epworth Sleepiness Scale ≥10. Fatigue severity was assessed with the Beck Depression Inventory-2. 208 participants had EDS, 27 had significant fatigue, and 11 had both. Participants with EDS or fatigue had significantly lower cognitive scores, more disturbed sleep, and medical comorbidities. The presence of EDS was associated with both global and regional atrophy, whereas fatigue was more associated with frontal and temporal changes. Cortical thinning predicted by EDS and fatigue was maximal in the temporal region with average reduction of 34.2 μm (95% CI, -54.1, -14.3; P = 0.001) and 90.2 μm (95% CI, -142.1, -38.2; P = 0.001), respectively. Fatigue was also associated with hippocampal volume reduction of -374.2 mm(3) (95% CI, -670.8, -77.7; P = 0.013). Temporal cortical thinning predicted by presence of EDS and fatigue was equivalent to more than 3.5 and 9 additional years of aging, respectively. EDS and fatigue were associated with cortical thickness reduction primarily in regions with increased age-susceptibility, which may indicate accelerated brain aging.

  7. Antiaging Effect of Metformin on Brain in Naturally Aged and Accelerated Senescence Model of Rat.

    PubMed

    Garg, Geetika; Singh, Sandeep; Singh, Abhishek Kumar; Rizvi, Syed Ibrahim

    2017-01-09

    Metformin, a biguanide, is a widely used antidiabetic drug, which inhibits gluconeogenesis and is used to treat hyperglycemia in type 2 diabetes. Through activation of AMPK (AMP-activated protein kinase) pathway, metformin also mimics caloric restriction health benefits. Aging causes substantial molecular to morphological changes in brain, the brain cells being more susceptible toward oxidative stress mediated damages due to the presence of high lipid content and higher oxygen consumption. Wistar rats (naturally aged and d-galactose induced rat model) were supplemented with metformin (300 mg/kg b.w. orally) for 6 weeks. The biomarkers of oxidative stress such as antioxidant capacity (ferric reducing antioxidant potential [FRAP]), malondialdehyde (MDA), reduced glutathione (GSH), protein carbonyl (PCO), reactive oxygen species (ROS), acetylcholinesterase (AChE) activity, and nitric oxide (NO) were measured in brain tissues of control and experimental groups. The results indicate that metformin treatment augmented the levels of FRAP and GSH in naturally aged, and d-gal induced aging model groups compared to the respective controls. In contrast, metformin treated groups exhibited significant reduction in MDA, PCO, ROS, and NO levels and a significant increase in AChE activity in induced aging rats. The administration of d-galactose upregulated the expression of sirtuin-2, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) and downregulated the expression of Beclin-1. Metformin supplementation downregulated the d-galactose induced expressions of sirtuin-2, IL-6, and TNF-α expression, whereas upregulated the Beclin-1 expression. Our data confirm that metformin restores the antioxidant status and improves healthy brain aging through the activation of autophagy and reduction in inflammation.

  8. Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats.

    PubMed

    Ho, Yuen-Shan; Yang, Xifei; Yeung, Sze-Chun; Chiu, Kin; Lau, Chi-Fai; Tsang, Andrea Wing-Ting; Mak, Judith Choi-Wo; Chang, Raymond Chuen-Chung

    2012-01-01

    Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD). To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD) rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP) processing by increasing the production of sAPPβ and accumulation of β-amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia.

  9. Menopause accelerates biological aging

    PubMed Central

    Levine, Morgan E.; Lu, Ake T.; Chen, Brian H.; Hernandez, Dena G.; Singleton, Andrew B.; Ferrucci, Luigi; Bandinelli, Stefania; Salfati, Elias; Manson, JoAnn E.; Quach, Austin; Kusters, Cynthia D. J.; Kuh, Diana; Wong, Andrew; Teschendorff, Andrew E.; Widschwendter, Martin; Ritz, Beate R.; Absher, Devin; Assimes, Themistocles L.; Horvath, Steve

    2016-01-01

    Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the “epigenetic clock”), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further. PMID:27457926

  10. Neurodegeneration in accelerated aging.

    PubMed

    Scheibye-Knudsen, Moren

    2016-11-01

    The growing proportion of elderly people represents an increasing economic burden, not least because of age-associated diseases that pose a significant cost to the health service. Finding possible interventions to age-associated disorders therefore have wide ranging implications. A number of genetically defined accelerated aging diseases have been characterized that can aid in our understanding of aging. Interestingly, all these diseases are associated with defects in the maintenance of our genome. A subset of these disorders, Cockayne syndrome, Xeroderma pigmentosum group A and ataxia-telangiectasia, show neurological involvement reminiscent of what is seen in primary human mitochondrial diseases. Mitochondria are the power plants of the cells converting energy stored in oxygen, sugar, fat, and protein into ATP, the energetic currency of our body. Emerging evidence has linked this organelle to aging and finding mitochondrial dysfunction in accelerated aging disorders thereby strengthens the mitochondrial theory of aging. This theory states that an accumulation of damage to the mitochondria may underlie the process of aging. Indeed, it appears that some accelerated aging disorders that show neurodegeneration also have mitochondrial dysfunction. The mitochondrial alterations may be secondary to defects in nuclear DNA repair. Indeed, nuclear DNA damage may lead to increased energy consumption, alterations in mitochondrial ATP production and defects in mitochondrial recycling, a term called mitophagy. These changes may be caused by activation of poly-ADP-ribose-polymerase 1 (PARP1), an enzyme that responds to DNA damage. Upon activation PARP1 utilizes key metabolites that attenuate pathways that are normally protective for the cell. Notably, pharmacological inhibition of PARP1 or reconstitution of the metabolites rescues the changes caused by PARP1 hyperactivation and in many cases reverse the phenotypes associated with accelerated aging. This implies that modulation

  11. Exposure to radiation accelerates normal brain aging and produces deficits in spatial learning and memory

    NASA Astrophysics Data System (ADS)

    Shukitt-Hale, B.; Casadesus, G.; Carey, A.; Rabin, B. M.; Joseph, J. A.

    Previous studies have shown that radiation exposure, particularly to particles of high energy and charge (HZE particles), produces deficits in spatial learning and memory. These adverse behavioral effects are similar to those seen in aged animals. It is possible that these shared effects may be produced by the same mechanism; oxidative stress damage to the central nervous system caused by an increased release of reactive oxygen species is likely responsible for the deficits seen in aging and following irradiation. Both aged and irradiated rats display cognitive impairment in tests of spatial learning and memory such as the Morris water maze and the radial arm maze. These rats have decrements in the ability to build spatial representations of the environment and they utilize non-spatial strategies to solve tasks. Furthermore, they show a lack of spatial preference, due to a decline in the ability to process or retain place (position of a goal with reference to a "map" provided by the configuration of numerous cues in the environment) information. These declines in spatial memory occur in measures dependent on both reference and working memory, and in the flexibility to reset mental images. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere. Supported by NASA Grants NAG9-1190 and NAG9-1529

  12. Chronic acceleration and brain density

    NASA Technical Reports Server (NTRS)

    Hoffman, L. F.; Smith, A. H.

    1982-01-01

    Tests carried out on rabbits show that the effect of chronic acceleration is not uniform among the various tissues studied. Although body mass is reduced by the treatment, as expected, no change is apparent in brain mass or in the density of cerebrospinal fluid. Acceleration-induced changes are encountered in tissue density, the myocardium exhibiting a transient increase followed by an exponential decrease toward a limit and the brain showing an arithmetic increase in density with continued exposure to 2.5 G. The data are seen as suggesting that a specific brain load is not a regulated phenomenon and that no physiological processes occur to attenuate the increased load imposed by the hyperdynamic environment. An equation is derived indicating that the stimulus potential per unit of brain load increases with body size, even though brain density decreases and cerebrospinal fluid density increases.

  13. Age-related alterations in the expression of glial cell line-derived neurotrophic factor in the senescence-accelerated mouse brain.

    PubMed

    Miyazaki, Hiroyuki; Okuma, Yasunobu; Nomura, Jun; Nagashima, Kazuo; Nomura, Yasuyuki

    2003-05-01

    Senescence-accelerated mouse prone 8 (SAMP8) and prone 10 (SAMP10) are useful murine model of accelerated aging. SAMP8 shows marked impairment of learning and memory, whereas SAMP10 shows brain atrophy and aging-associated depressive behavior. This study examined the expression of glial cell line-derived neurotrophic factor (GDNF) in SAMP8 and SAMP10 brains, relative to that in SAM resistant 1 (SAMR1) controls, which age normally. Hippocampal GDNF mRNA expression decreased in an age-dependent manner (10- vs 2-month-old animals) in the SAMR1, but not in the SAMP8 or SAMP10 strains. Furthermore, GDNF mRNA expression in 2-month-old SAMP8 and SAMP10 strains was less than in SAMR1 specimens of the same age. The number of surviving neurons in the CA1 region decreased with age in SAMP8 and SAMP10, and also decreased relative to the number of neurons in 10-month-old SAMR1 controls. Immunohistochemistry revealed that cells that were positive for GDNF-like activity in 10-month-old SAMP8 and SAMP10 were diffusely distributed, in part, around the pyramidal cell layer in the hippocampus. These findings suggest that low GDNF expression in young SAMP8 and SAMP10 may be involved in hippocampal dysfunctions, such as age-related learning impairment and neuronal death.

  14. Neuroprotective effect of hydroalcoholic extract of dried fruits of Trapa bispinosa Roxb on lipofuscinogenesis and fluorescence product in brain of D-galactose induced ageing accelerated mice.

    PubMed

    Ambikar, D B; Harle, U N; Khandare, R A; Bore, V V; Vyawahare, N S

    2010-04-01

    Effect of hydroalcoholic extract T. bispinosa (TB) was studied on fluorescence product and biochemical parameter like lipid peroxidation, catalase activity and glutathione peroxidase activity in the brain of female albino mice. Ageing was accelerated by the treatment of 0.5 ml 5% D-galactose for 15 days. This resulted in increased fluorescence product, increase lipid peroxidation and decrease antioxidant enzyme like glutathione peroxides and catalase in cerebral cortex. After cotreatment with hydroalcoholic extract of TB (500 mg/kg, po) there was decrease in fluorescence product in cerebral cortex. Moreover, TB inhibited increase lipid peroxidation and restores glutathione peroxidase and catalase activity in cerebral cortex as compare to ageing accelerated control group. To conclude TB found to be effective antioxidative agent which could to some extent reverse D-galactose induced ageing changes resulted due to oxidative damage.

  15. Chronic Porphyromonas gingivalis infection accelerates the occurrence of age-related granules in ApoE– / – mice brains

    PubMed Central

    Singhrao, Sim K.; Chukkapalli, Sasanka; Poole, Sophie; Velsko, Irina; Crean, St John; Kesavalu, Lakshmyya

    2017-01-01

    ABSTRACT This study explored the origin of age-related granules in the apolipoprotein E gene knockout (ApoE−/−) B6 background mice brains following chronic gingival infection with Porphyromonas gingivalis for 24 weeks. Intracerebral localization of P. gingivalis was detected by fluorescence in situ hybridization (FISH) and its protease by immunohistochemistry. The age-related granules were observed by periodic acid–Schiff (PAS), silver impregnation, and immunostaining. FISH showed intracerebral dissemination of P. gingivalis cells (p = 0.001). PAS and silver impregnation demonstrated the presence of larger inclusions restricted to the CA1, CA2, and dentate gyrus sectors of the hippocampus. A specific monoclonal antibody to bacterial peptidoglycan detected clusters of granules with variable sizes in mice brains infected with P. gingivalis (p = 0.004), and also highlighted areas of diffuse punctate staining equating to physical tissue damage. Mouse immunoglobulin G was observed in the capillaries of the cerebral parenchyma of all P. gingivalis–infected brains (p = 0.001), and on pyramidal neurons in some severely affected mice, compared with the sham-infected mice. Gingipains was also observed in microvessels of the hippocampus in the infected mice. This study supports the possibility of early appearance of age-related granules in ApoE−/− mice following inflammation-mediated tissue injury, accompanied by loss of cerebral blood-brain barrier integrity. PMID:28326151

  16. Is biological aging accelerated in drug addiction?

    PubMed

    Bachi, Keren; Sierra, Salvador; Volkow, Nora D; Goldstein, Rita Z; Alia-Klein, Nelly

    2017-02-01

    Drug-addiction may trigger early onset of age-related disease, due to drug-induced multi-system toxicity and perilous lifestyle, which remains mostly undetected and untreated. We present the literature on pathophysiological processes that may hasten aging and its relevance to addiction, including: oxidative stress and cellular aging, inflammation in periphery and brain, decline in brain volume and function, and early onset of cardiac, cerebrovascular, kidney, and liver disease. Timely detection of accelerated aging in addiction is crucial for the prevention of premature morbidity and mortality.

  17. Nutrients, Microglia Aging, and Brain Aging.

    PubMed

    Wu, Zhou; Yu, Janchun; Zhu, Aiqin; Nakanishi, Hiroshi

    2016-01-01

    As the life expectancy continues to increase, the cognitive decline associated with Alzheimer's disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of "microglia aging." This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging.

  18. Nutrients, Microglia Aging, and Brain Aging

    PubMed Central

    Wu, Zhou; Yu, Janchun; Zhu, Aiqin; Nakanishi, Hiroshi

    2016-01-01

    As the life expectancy continues to increase, the cognitive decline associated with Alzheimer's disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of “microglia aging.” This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging. PMID:26941889

  19. Accelerated epigenetic aging in Down syndrome

    PubMed Central

    Horvath, Steve; Garagnani, Paolo; Bacalini, Maria Giulia; Pirazzini, Chiara; Salvioli, Stefano; Gentilini, Davide; Di Blasio, Anna Maria; Giuliani, Cristina; Tung, Spencer; Vinters, Harry V; Franceschi, Claudio

    2015-01-01

    Down Syndrome (DS) entails an increased risk of many chronic diseases that are typically associated with older age. The clinical manifestations of accelerated aging suggest that trisomy 21 increases the biological age of tissues, but molecular evidence for this hypothesis has been sparse. Here, we utilize a quantitative molecular marker of aging (known as the epigenetic clock) to demonstrate that trisomy 21 significantly increases the age of blood and brain tissue (on average by 6.6 years, P = 7.0 × 10−14). PMID:25678027

  20. Is schizophrenia a syndrome of accelerated aging?

    PubMed

    Kirkpatrick, Brian; Messias, Erick; Harvey, Philip D; Fernandez-Egea, Emilio; Bowie, Christopher R

    2008-11-01

    Schizophrenia is associated with a number of anatomical and physiological abnormalities outside of the brain, as well as with a decrease in average life span estimated at 20% in the United States. Some studies suggest that this increased mortality is not entirely due to associated causes such as suicide and the use of psychotropic medications. In this article, in order to focus greater attention on the increased mortality associated with schizophrenia, we present a special case of the hypothesis that physiological abnormalities associated with schizophrenia make a contribution to the increased mortality of schizophrenia: specifically, the hypothesis that schizophrenia is a syndrome of accelerated aging. Evidence consistent with this hypothesis comes from several areas. The biological plausibility of the hypothesis is supported by the existence of established syndromes of accelerated aging and by the sharing of risk factors between schizophrenia and other age-related conditions. We propose methods for testing the hypothesis.

  1. Epigenetic Age Acceleration Assessed With Human White-Matter Images.

    PubMed

    Hodgson, Karen; Carless, Melanie A; Kulkarni, Hemant; Curran, Joanne E; Sprooten, Emma; Knowles, Emma E; Mathias, Samuel; Göring, Harald Hh; Yao, Nailin; Olvera, Rene L; Fox, Peter T; Almasy, Laura; Duggirala, Ravi; Blangero, John; Glahn, David C

    2017-04-06

    The accurate estimation of age using methylation data has proved a useful and heritable biomarker, with acceleration in epigenetic age predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are also heritable and highly sensitive to both normal and pathological aging processes across adulthood. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity in humans. Our goal was to investigate processes that underlie inter-individual variability in age-related changes in the brain. Using blood taken from a Mexican-American extended pedigree sample (n=628; age=23.28-93.11 years), epigenetic age was estimated using the method developed by S. Horvath (2013). For n=376 individuals, DTI scans were also available. The interrelationship between epigenetic age acceleration and global white matter integrity were investigated with variance decomposition methods. To test for neuroanatomical specificity, 16 specific tracts were additionally considered. We observed negative phenotypic correlations between epigenetic age acceleration and global white matter tract integrity (ρpheno=-0.119, p=0.028), with evidence of shared genetic (ρgene=-0.463, p=0.013) but not environmental influences. Negative phenotypic and genetic correlations with age acceleration were also seen for a number of specific white matter tracts, along with additional negative phenotypic correlations between granulocyte abundance and white matter integrity. These findings that increased acceleration in epigenetic age in peripheral blood correlates with reduced white matter integrity in the brain, and shares common genetic influences. provide a window into the neurobiology of aging processes within the brain and a potential biomarker of normal and pathological brain aging.SIGNIFICANCE STATEMENTEpigenetic measures can be used to predict age with a high degree of accuracy and so capture acceleration in biological age

  2. Exposure to 56Fe irradiation accelerates normal brain aging and produces deficits in spatial learning and memory

    NASA Astrophysics Data System (ADS)

    Shukitt-Hale, Barbara; Casadesus, Gemma; Carey, Amanda N.; Rabin, Bernard M.; Joseph, James A.

    Previous studies have shown that radiation exposure, particularly to particles of high energy and charge (HZE particles) such as 56Fe, produces deficits in spatial learning and memory. These adverse behavioral effects are similar to those seen in aged animals. It is possible that these shared effects may be produced by the same mechanism. For example, an increased release of reactive oxygen species, and the subsequent oxidative stress and inflammatory damage caused to the central nervous system, is likely responsible for the deficits seen in aging and following irradiation. Therefore, dietary antioxidants, such as those found in fruits and vegetables, could be used as countermeasures to prevent the behavioral changes seen in these conditions. Both aged and irradiated rats display cognitive impairment in tests of spatial learning and memory such as the Morris water maze and the radial arm maze. These rats have decrements in the ability to build spatial representations of the environment, and they utilize non-spatial strategies to solve tasks. Furthermore, they show a lack of spatial preference, due to a decline in the ability to process or retain place (position of a goal with reference to a “map” provided by the configuration of numerous cues in the environment) information. These declines in spatial memory occur in measures dependent on both reference and working memory, and in the flexibility to reset mental images. These results show that irradiation with 56Fe high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts, particularly middle-aged ones, to perform critical tasks during long-term space travel beyond the magnetosphere.

  3. Antisense directed against PS-1 gene decreases brain oxidative markers in aged senescence accelerated mice (SAMP8) and reverses learning and memory impairment: a proteomics study.

    PubMed

    Fiorini, Ada; Sultana, Rukhsana; Förster, Sarah; Perluigi, Marzia; Cenini, Giovanna; Cini, Chiara; Cai, Jian; Klein, Jon B; Farr, Susan A; Niehoff, Michael L; Morley, John E; Kumar, Vijaya B; Allan Butterfield, D

    2013-12-01

    Amyloid β-peptide (Aβ) plays a central role in the pathophysiology of Alzheimer's disease (AD) through the induction of oxidative stress. This peptide is produced by proteolytic cleavage of amyloid precursor protein (APP) by the action of β- and γ-secretases. Previous studies demonstrated that reduction of Aβ, using an antisense oligonucleotide (AO) directed against the Aβ region of APP, reduced oxidative stress-mediated damage and prevented or reverted cognitive deficits in senescence-accelerated prone mice (SAMP8), a useful animal model for investigating the events related to Aβ pathology and possibly to the early phase of AD. In the current study, aged SAMP8 were treated by AO directed against PS-1, a component of the γ-secretase complex, and tested for learning and memory in T-maze foot shock avoidance and novel object recognition. Brain tissue was collected to identify the decrease of oxidative stress and to evaluate the proteins that are differently expressed and oxidized after the reduction in free radical levels induced by Aβ. We used both expression proteomics and redox proteomics approaches. In brain of AO-treated mice a decrease of oxidative stress markers was found, and the proteins identified by proteomics as expressed differently or nitrated are involved in processes known to be impaired in AD. Our results suggest that the treatment with AO directed against PS-1 in old SAMP8 mice reverses learning and memory deficits and reduces Aβ-mediated oxidative stress with restoration to the normal condition and identifies possible pharmacological targets to combat this devastating dementing disease.

  4. Resonance of human brain under head acceleration

    PubMed Central

    Laksari, Kaveh; Wu, Lyndia C.; Kurt, Mehmet; Kuo, Calvin; Camarillo, David C.

    2015-01-01

    Although safety standards have reduced fatal head trauma due to single severe head impacts, mild trauma from repeated head exposures may carry risks of long-term chronic changes in the brain's function and structure. To study the physical sensitivities of the brain to mild head impacts, we developed the first dynamic model of the skull–brain based on in vivo MRI data. We showed that the motion of the brain can be described by a rigid-body with constrained kinematics. We further demonstrated that skull–brain dynamics can be approximated by an under-damped system with a low-frequency resonance at around 15 Hz. Furthermore, from our previous field measurements, we found that head motions in a variety of activities, including contact sports, show a primary frequency of less than 20 Hz. This implies that typical head exposures may drive the brain dangerously close to its mechanical resonance and lead to amplified brain–skull relative motions. Our results suggest a possible cause for mild brain trauma, which could occur due to repetitive low-acceleration head oscillations in a variety of recreational and occupational activities. PMID:26063824

  5. Increased brain-predicted aging in treated HIV disease

    PubMed Central

    Underwood, Jonathan; Caan, Matthan W.A.; De Francesco, Davide; van Zoest, Rosan A.; Leech, Robert; Wit, Ferdinand W.N.M.; Portegies, Peter; Geurtsen, Gert J.; Schmand, Ben A.; Schim van der Loeff, Maarten F.; Franceschi, Claudio; Sabin, Caroline A.; Majoie, Charles B.L.M.; Winston, Alan; Reiss, Peter; Sharp, David J.

    2017-01-01

    Objective: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. Methods: A large sample of virologically suppressed HIV-positive adults (n = 162, age 45–82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18–90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age − chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. Results: HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (−0.87 ± 8.40 years; b = 3.48, p < 0.01). Increased brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Conclusion: Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. PMID:28258081

  6. Ageing, neurodegeneration and brain rejuvenation

    PubMed Central

    2016-01-01

    Although systemic diseases take the biggest toll on human health and well-being, increasingly, a failing brain is the arbiter of a death preceded by a gradual loss of the essence of being. Ageing, which is fundamental to neurodegeneration and dementia, affects every organ in the body and seems to be encoded partly in a blood-based signature. Indeed, factors in the circulation have been shown to modulate ageing and to rejuvenate numerous organs, including the brain. The discovery of such factors, the identification of their origins and a deeper understanding of their functions is ushering in a new era in ageing and dementia research. PMID:27830812

  7. Obesity accelerates epigenetic aging of human liver.

    PubMed

    Horvath, Steve; Erhart, Wiebke; Brosch, Mario; Ammerpohl, Ole; von Schönfels, Witigo; Ahrens, Markus; Heits, Nils; Bell, Jordana T; Tsai, Pei-Chien; Spector, Tim D; Deloukas, Panos; Siebert, Reiner; Sipos, Bence; Becker, Thomas; Röcken, Christoph; Schafmayer, Clemens; Hampe, Jochen

    2014-10-28

    Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an "epigenetic clock") to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10(-4) in dataset 1 and r = 0.42, P = 1.2 × 10(-4) in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10(-9)) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer.

  8. Accelerate Genomic Aging in Congenital Neutropenia

    DTIC Science & Technology

    2015-08-01

    myeloid leukemia (AML) is perhaps the major clinical concern in patients with severe congenital neutropenia (SCN) and Shwachman- Diamond syndrome (SDS... Diamond syndrome (SDS), cyclic neutropenia, or age-matched healthy controls. Aim 2. To determine whether increased G-CSF signaling accelerates the...agents, such as radiation. 2. KEYWORDS Congenital neutropenia Severe congenital neutropenia Shwachman Diamond syndrome Cyclic neutropenia

  9. Cognitive deterioration in adult epilepsy: Does accelerated cognitive ageing exist?

    PubMed

    Breuer, L E M; Boon, P; Bergmans, J W M; Mess, W H; Besseling, R M H; de Louw, A; Tijhuis, A G; Zinger, S; Bernas, A; Klooster, D C W; Aldenkamp, A P

    2016-05-01

    A long-standing concern has been whether epilepsy contributes to cognitive decline or so-called 'epileptic dementia'. Although global cognitive decline is generally reported in the context of chronic refractory epilepsy, it is largely unknown what percentage of patients is at risk for decline. This review is focused on the identification of risk factors and characterization of aberrant cognitive trajectories in epilepsy. Evidence is found that the cognitive trajectory of patients with epilepsy over time differs from processes of cognitive ageing in healthy people, especially in adulthood-onset epilepsy. Cognitive deterioration in these patients seems to develop in a 'second hit model' and occurs when epilepsy hits on a brain that is already vulnerable or vice versa when comorbid problems develop in a person with epilepsy. Processes of ageing may be accelerated due to loss of brain plasticity and cognitive reserve capacity for which we coin the term 'accelerated cognitive ageing'. We believe that the concept of accelerated cognitive ageing can be helpful in providing a framework understanding global cognitive deterioration in epilepsy.

  10. Brain trace elements and aging

    NASA Astrophysics Data System (ADS)

    Hebbrecht, Geert; Maenhaut, Willy; Reuck, Jacques De

    1999-04-01

    Degenerative mechanisms involved in the aging process of the brain are to a certain extent counteracted by repair mechanisms. In both degenerative and recovery processes, trace elements are involved. The present study focused on the role of two minor (i.e., K and Ca) and six trace elements (i.e., Mn, Fe, Cu, Zn, Se and Rb) in the aging process. The elements were determined by PIXE in cerebral cortex and white matter, basal ganglia, brainstem and cerebellar cortex of 18 postmortem human brains, from persons without a history of neurologic or psychiatric disease who deceased between the age of 7 and 79. This age range allowed us to study the relationship between elemental concentrations and age. The most prominent findings were a concentration decrease for K and Rb and a concentration increase for the elements Ca, Fe, Zn and Se. The study supports recent findings that Ca and Fe are involved in brain degenerative processes initiated by oxygen free radicals, whereas Zn and Se are involved in immunological reactions counteracting the aging process.

  11. Neuroethics in the Age of Brain Projects.

    PubMed

    Greely, Henry T; Ramos, Khara M; Grady, Christine

    2016-11-02

    Neuroscience advances have brought important ethical questions. The recent launch of two large brain projects, the United States BRAIN Initiative and the European Union Human Brain Project, should accelerate progress in understanding the brain. This article examines neuroethics in those two projects, as well as its exploration by other efforts.

  12. Aging and functional brain networks

    SciTech Connect

    Tomasi D.; Tomasi, D.; Volkow, N.D.

    2011-07-11

    Aging is associated with changes in human brain anatomy and function and cognitive decline. Recent studies suggest the aging decline of major functional connectivity hubs in the 'default-mode' network (DMN). Aging effects on other networks, however, are largely unknown. We hypothesized that aging would be associated with a decline of short- and long-range functional connectivity density (FCD) hubs in the DMN. To test this hypothesis, we evaluated resting-state data sets corresponding to 913 healthy subjects from a public magnetic resonance imaging database using functional connectivity density mapping (FCDM), a voxelwise and data-driven approach, together with parallel computing. Aging was associated with pronounced long-range FCD decreases in DMN and dorsal attention network (DAN) and with increases in somatosensory and subcortical networks. Aging effects in these networks were stronger for long-range than for short-range FCD and were also detected at the level of the main functional hubs. Females had higher short- and long-range FCD in DMN and lower FCD in the somatosensory network than males, but the gender by age interaction effects were not significant for any of the networks or hubs. These findings suggest that long-range connections may be more vulnerable to aging effects than short-range connections and that, in addition to the DMN, the DAN is also sensitive to aging effects, which could underlie the deterioration of attention processes that occurs with aging.

  13. Accelerated aging in the tumor microenvironment

    PubMed Central

    Martinez-Outschoorn, Ubaldo E; Pavlides, Stephanos; Whitaker-Menezes, Diana; Pestell, Richard G; Howell, Anthony

    2011-01-01

    Cancer is thought to be a disease associated with aging. Interestingly, normal aging is driven by the production of ROS and mitochondrial oxidative stress, resulting in the cumulative accumulation of DNA damage. Here, we discuss how ROS signaling, NFκB- and HIF1-activation in the tumor micro-environment induces a form of “accelerated aging,” which leads to stromal inflammation and changes in cancer cell metabolism. Thus, we present a unified model where aging (ROS), inflammation (NFκB) and cancer metabolism (HIF1), act as co-conspirators to drive autophagy (“self-eating”) in the tumor stroma. Then, autophagy in the tumor stroma provides high-energy “fuel” and the necessary chemical building blocks, for accelerated tumor growth and metastasis. Stromal ROS production acts as a “mutagenic motor” and allows cancer cells to buffer—at a distance—exactly how much of a mutagenic stimulus they receive, further driving tumor cell selection and evolution. Surviving cancer cells would be selected for the ability to induce ROS more effectively in stromal fibroblasts, so they could extract more nutrients from the stroma via autophagy. If lethal cancer is a disease of “accelerated host aging” in the tumor stroma, then cancer patients may benefit from therapy with powerful antioxidants. Antioxidant therapy should block the resulting DNA damage, and halt autophagy in the tumor stroma, effectively “cutting off the fuel supply” for cancer cells. These findings have important new implications for personalized cancer medicine, as they link aging, inflammation and cancer metabolism with novel strategies for more effective cancer diagnostics and therapeutics. PMID:21654190

  14. Insights into accelerated aging of SSL luminaires

    SciTech Connect

    Davis, J. Lynn; Lamvik, Michael; Bittle, James; Shepherd, Sarah; Yaga, Robert; Baldasaro, Nick; Solano, Eric; Bobashev, Georgiy

    2013-09-30

    Although solid-state lighting (SSL) products are often intended to have product lifetimes of 15 years or more, the rapid change in technology has created a need for accelerated life tests (ALTs) that can be performed in the span of several months. A critical element of interpreting results from any systems-level ALT is understanding of the impact of the test environment on each component. Because of its ubiquity in electronics, the use of temperature-humidity environments as potential ALTs for SSL luminaires was investigated. Results from testing of populations of three commercial 6” downlights in environments of 85oC and 85% relative humidity (RH) and 75oC and 75% RH are reported. These test environments were found to accelerate lumen depreciation of the entire luminaire optical system, including LEDs, lenses, and reflectors. The effects of aging were found to depend strongly on both the optical materials that were used and the design of the luminaire; this shows that the lumen maintenance behavior of SSL luminaires must be addressed at the optical systems level. Temperature-Humidity ALTs can be a useful test in understand lumainaire depreciation provided that proper consideration is given to the different aging rates of various materials. Since the impact of the temperature-humidity environment varies among components of the optical system, uniform aging of all system components in a single test is difficult to achieve.

  15. Insights into accelerated aging of SSL luminaires

    DOE PAGES

    Davis, J. Lynn; Lamvik, Michael; Bittle, James; ...

    2013-09-30

    Although solid-state lighting (SSL) products are often intended to have product lifetimes of 15 years or more, the rapid change in technology has created a need for accelerated life tests (ALTs) that can be performed in the span of several months. A critical element of interpreting results from any systems-level ALT is understanding of the impact of the test environment on each component. Because of its ubiquity in electronics, the use of temperature-humidity environments as potential ALTs for SSL luminaires was investigated. Results from testing of populations of three commercial 6” downlights in environments of 85oC and 85% relative humiditymore » (RH) and 75oC and 75% RH are reported. These test environments were found to accelerate lumen depreciation of the entire luminaire optical system, including LEDs, lenses, and reflectors. The effects of aging were found to depend strongly on both the optical materials that were used and the design of the luminaire; this shows that the lumen maintenance behavior of SSL luminaires must be addressed at the optical systems level. Temperature-Humidity ALTs can be a useful test in understand lumainaire depreciation provided that proper consideration is given to the different aging rates of various materials. Since the impact of the temperature-humidity environment varies among components of the optical system, uniform aging of all system components in a single test is difficult to achieve.« less

  16. Insights into accelerated aging of SSL luminaires

    NASA Astrophysics Data System (ADS)

    Davis, J. Lynn; Lamvik, Michael; Bittle, James; Shepherd, Sarah; Yaga, Robert; Baldasaro, Nick; Solano, Eric; Bobashev, Georgiy

    2013-09-01

    Although solid-state lighting (SSL) products are often intended to have product lifetimes of 15 years or more, the rapid change in technology has created a need for accelerated life tests (ALTs) that can be performed in the span of several months. A critical element of interpreting results from any systems-level ALT is understanding of the impact of the test environment on each component. Because of its ubiquity in electronics, the use of temperature-humidity environments as potential ALTs for SSL luminaires was investigated. Results from testing of populations of three commercial 6" downlights in environments of 85°C and 85% relative humidity (RH) and 75°C and 75% RH are reported. These test environments were found to accelerate lumen depreciation of the entire luminaire optical system, including LEDs, lenses, and reflectors. The effects of aging were found to depend strongly on both the optical materials that were used and the design of the luminaire; this shows that the lumen maintenance behavior of SSL luminaires must be addressed at the optical systems level. Temperature-Humidity ALTs can be a useful test in understand lumainaire depreciation provided that proper consideration is given to the different aging rates of various materials. Since the impact of the temperature-humidity environment varies among components of the optical system, uniform aging of all system components in a single test is difficult to achieve.

  17. Accelerated Aging in Electrolytic Capacitors for Prognostics

    NASA Technical Reports Server (NTRS)

    Celaya, Jose R.; Kulkarni, Chetan; Saha, Sankalita; Biswas, Gautam; Goebel, Kai Frank

    2012-01-01

    The focus of this work is the analysis of different degradation phenomena based on thermal overstress and electrical overstress accelerated aging systems and the use of accelerated aging techniques for prognostics algorithm development. Results on thermal overstress and electrical overstress experiments are presented. In addition, preliminary results toward the development of physics-based degradation models are presented focusing on the electrolyte evaporation failure mechanism. An empirical degradation model based on percentage capacitance loss under electrical overstress is presented and used in: (i) a Bayesian-based implementation of model-based prognostics using a discrete Kalman filter for health state estimation, and (ii) a dynamic system representation of the degradation model for forecasting and remaining useful life (RUL) estimation. A leave-one-out validation methodology is used to assess the validity of the methodology under the small sample size constrain. The results observed on the RUL estimation are consistent through the validation tests comparing relative accuracy and prediction error. It has been observed that the inaccuracy of the model to represent the change in degradation behavior observed at the end of the test data is consistent throughout the validation tests, indicating the need of a more detailed degradation model or the use of an algorithm that could estimate model parameters on-line. Based on the observed degradation process under different stress intensity with rest periods, the need for more sophisticated degradation models is further supported. The current degradation model does not represent the capacitance recovery over rest periods following an accelerated aging stress period.

  18. Infant's DNA Methylation Age at Birth and Epigenetic Aging Accelerators

    PubMed Central

    Chen, Weidan; Lin, Fangqin

    2016-01-01

    Knowing the biological age of the neonates enables us to evaluate and better understand the health and maturity comprehensively. However, because of dearth of biomarkers, it is difficult to quantify the neonatal biological age. Here we sought to quantify and assess the variability in biological age at birth and to better understand how the aging rates before birth are influenced by exposure in intrauterine period by employing a novel epigenetic biomarker of aging (epigenetic clock). We observed that the methylation age at birth was independent of the infant's sex but was significantly influenced by race. Partial correlation analysis showed a significant negative relationship between maternal socioeconomic status and infants' methylation age (rs = −0.48, Ps = 0.005). A significant association with the risk of fast aging was observed for prenatal exposure to tobacco smoke with OR (95% CI) of 3.17 (1.05–9.56). Both estimated cell abundance measures and lymphocyte subpopulations in cord blood showed that tobacco exposed group exhibit an altered T cell compartment, specifically substantial loss of naive T cells. Present study provides the first evidence that common perinatal exposure (such as maternal smoking and lower socioeconomic status) may be important aging accelerators and substantial loss of naive T cells may play a role in the smoking-related fast aging phenomenon. PMID:28058257

  19. Accelerated Aging of Lead-Free Propellant

    NASA Technical Reports Server (NTRS)

    Furrow, Keith W.; Jervey, David D.

    2000-01-01

    Following higher than expected 2-NDPA depletion rates in a lead-free doublebase formulation (RPD-422), an accelerated aging study was conducted to verify the depletion rates. A test plan was prepared to compare the aging characteristics of lead-free propellant and NOSIH-AA2. The study was also designed to determine which lead-free ballistic modifiers accelerated 2-NDPA depletion. The increased depletion rate occurred in propellants containing monobasic copper salicylate. Four lead-free propellants were then formulated to improved aging characteristics over previous lead-free propellant formulations. The new formulations reduced or replaced the monobasic copper salicylate. The new formulations had improved aging characteristics. Their burn rates, however, were unacceptable for use in a 2.75 inch rocket. To compare aging characteristics, stabilizer depletion rates of RPD-422, AA2, M28, and RLC 470/6A were measured or taken from the literature. The data were fit to a kinetic model. The model contained first and zero order terms which allowed the stabilizer concentration to go to zero. In the model, only the concentration of the primary stabilizer was considered. Derivatives beyond the first nitrated or nitroso derivative of 2-NPDA were not considered. The rate constants were fit to the Arrhenius equation and extrapolated to lower temperatures. The time to complete stabilizer depletion was estimated using the kinetic model. The four propellants were compared and the RPD-422 depleted faster at 45 C than both A22 and M28. These types of predictions depend on the validity of the model and on confidence in the Arrhenius relationship holding at lower temperatures. At 45 C, the zero order portion of the model dominates the depletion rate.

  20. [Glial activation and brain aging].

    PubMed

    Sugaya, K

    2001-10-01

    While basal forebrain cholinergic neurons degenerate in aging and Alzheimer's disease, the cholinergic groups of the upper brainstem are preserved. Since the brainstem reticular-like cholinergic neurons differ from the rostral cholinergic phenotype by their high expression of nitric oxide synthase (NOS) mRNA, we hypothesized that they contain biochemical mechanisms to protect themselves against self-induced damage by nitric oxide (NO). Our initial question was a source of the NO during the aging process. We found a significant correlation between cognitive function and markers for glial activation and oxidative stress using aged rats. This result indicates that oxidative stress accompanied by glial activation may be occurred in the cognitively impaired animals. We also found mitochondrial DNA (mDNA) was significantly damaged in these animals, while accumulation of oxidative damage was not evident in other molecules. Therefore, oxidative damage to the mDNA by glial activation may occur in the cells having poor protection against oxidative stress during aging. Then the dysfunction of mitochondria, induced by the mDNA damage, may induce cell death as well as produce another oxidative stress to cause neuronal damage. The damaged neurons induce further glial activation and such self-accelerated immune-like response results in progressive neurodegeneration.

  1. US Particle Accelerators at Age 50.

    ERIC Educational Resources Information Center

    Wilson, R. R.

    1981-01-01

    Reviews the development of accelerators over the past 50 years. Topics include: types of accelerators, including cyclotrons; sociology of accelerators (motivation, financing, construction, and use); impact of war; national laboratories; funding; applications; future projects; foreign projects; and international collaborations. (JN)

  2. Successful brain aging: plasticity, environmental enrichment, and lifestyle.

    PubMed

    Mora, Francisco

    2013-03-01

    Aging is a physiological process that can develop without the appearance of concurrent diseases. However, very frequently, older people suffer from memory loss and an accelerated cognitive decline. Studies of the neurobiology of aging are beginning to decipher the mechanisms underlying not only the physiology of aging of the brain but also the mechanisms that make people more vulnerable to cognitive dysfunction and neurodegenerative diseases. Today we know that the aging brain retains a considerable functional plasticity, and that this plasticity is positively promoted by genes activated by different lifestyle factors. In this article some of these lifestyle factors and their mechanisms of action are reviewed, including environmental enrichment and the importance of food intake and some nutrients. Aerobic physical exercise and reduction of chronic stress are also briefly reviewed. It is proposed that lifestyle factors are powerful instruments to promote healthy and successful aging of the brain and delay the appearance of age-related cognitive deficits in elderly people.

  3. Staying Socially Active Nourishes the Aging Brain

    MedlinePlus

    ... fullstory_163679.html Staying Socially Active Nourishes the Aging Brain Researchers suggest making friends of all ages ... and Human Services. More Health News on: Healthy Aging Recent Health News Related MedlinePlus Health Topics Healthy ...

  4. Molecular aging of the brain, neuroplasticity, and vulnerability to depression and other brain-related disorders.

    PubMed

    Sibille, Etienne

    2013-03-01

    The increased risk for neurodegenerative and neuropsychiatric disorders associated with extended lifespan has long suggested mechanistic links between chronological age and brain-related disorders, including depression, Recent characterizations of age-dependent gene expression changes now show that aging of the human brain engages a specific set of biological pathways along a continuous lifelong trajectory, and that the same genes that are associated with normal brain aging are also frequently and similarly implicated in depression and other brain-related disorders. These correlative observations suggest a model of age-by-disease molecular interactions, in which brain aging promotes biological changes associated with diseases, and additional environmental factors and genetic variability contribute to defining disease risk or resiliency trajectories. Here we review the characteristic features of brain aging in terms of changes in gene function over time, and then focus on evidence supporting accelerated molecular aging in depression. This proposed age-by-disease biological interaction model addresses the current gap in research between "normal" brain aging and its connection to late-life diseases. The implications of this model are profound, as it provides an investigational framework for identifying critical moderating factors, outlines opportunities for early interventions or preventions, and may form the basis for a dimensional definition of diseases that goes beyond the current categorical system.

  5. Premature and accelerated aging: HIV or HAART?

    PubMed Central

    Smith, Reuben L.; de Boer, Richard; Brul, Stanley; Budovskaya, Yelena; van Spek, Hans

    2013-01-01

    Highly active antiretroviral therapy (HAART) has significantly increased life expectancy of the human immunodeficiency virus (HIV)-positive population. Nevertheless, the average lifespan of HIV-patients remains shorter compared to uninfected individuals. Immunosenescence, a current explanation for this difference invokes heavily on viral stimulus despite HAART efficiency in viral suppression. We propose here that the premature and accelerated aging of HIV-patients can also be caused by adverse effects of antiretroviral drugs, specifically those that affect the mitochondria. The nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral drug class for instance, is known to cause depletion of mitochondrial DNA via inhibition of the mitochondrial specific DNA polymerase-γ. Besides NRTIs, other antiretroviral drug classes such as protease inhibitors also cause severe mitochondrial damage by increasing oxidative stress and diminishing mitochondrial function. We also discuss important areas for future research and argue in favor of the use of Caenorhabditis elegans as a novel model system for studying these effects. PMID:23372574

  6. Accelerated Aging of Polymer Composite Bridge Materials

    SciTech Connect

    Carlson, Nancy Margaret; Blackwood, Larry Gene; Torres, Lucinda Laine; Rodriguez, Julio Gallardo; Yoder, Timothy Scott

    1999-03-01

    Accelerated aging research on samples of composite material and candidate ultraviolet (UV) protective coatings is determining the effects of six environmental factors on material durability. Candidate fastener materials are being evaluated to determine corrosion rates and crevice corrosion effects at load-bearing joints. This work supports field testing of a 30-ft long, 18-ft wide polymer matrix composite (PMC) bridge at the Idaho National Engineering and Environmental Laboratory (INEEL). Durability results and sensor data from tests with live loads provide information required for determining the cost/benefit measures to use in life-cycle planning, determining a maintenance strategy, establishing applicable inspection techniques, and establishing guidelines, standards, and acceptance criteria for PMC bridges for use in the transportation infrastructure.

  7. Accelerated aging syndromes, are they relevant to normal human aging?

    PubMed

    Dreesen, Oliver; Stewart, Colin L

    2011-09-01

    Hutchinson-Gilford Progeria (HGPS) and Werner syndromes are diseases that clinically resemble some aspects of accelerated aging. HGPS is caused by mutations in theLMNA gene resulting in post-translational processing defects that trigger Progeria in children. Werner syndrome, arising from mutations in the WRN helicase gene, causes premature aging in young adults. What are the molecular mechanism(s) underlying these disorders and what aspects of the diseases resemble physiological human aging? Much of what we know stems from the study of patient derived fibroblasts with both mutations resulting in increased DNA damage, primarily at telomeres. However, in vivo patients with Werner's develop arteriosclerosis, among other pathologies. In HGPS patients, including iPS derived cells from HGPS patients, as well as some mouse models for Progeria, vascular smooth muscle (VSM) appears to be among the most severely affected tissues. Defective Lamin processing, associated with DNA damage, is present in VSM from old individuals, indicating processing defects may be a factor in normal aging. Whether persistent DNA damage, particularly at telomeres, is the root cause for these pathologies remains to be established, since not all progeroid Lmna mutations result in DNA damage and genome instability.

  8. A Comparison of Accelerated and Non-accelerated MRI Scans for Brain Volume and Boundary Shift Integral Measures of Volume Change: Evidence from the ADNI Dataset.

    PubMed

    Manning, Emily N; Leung, Kelvin K; Nicholas, Jennifer M; Malone, Ian B; Cardoso, M Jorge; Schott, Jonathan M; Fox, Nick C; Barnes, Josephine

    2017-03-18

    The aim of this study was to assess whether the use of accelerated MRI scans in place of non-accelerated scans influenced brain volume and atrophy rate measures in controls and subjects with mild cognitive impairment and Alzheimer's disease. We used data from 861 subjects at baseline, 573 subjects at 6 months and 384 subjects at 12 months from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We calculated whole-brain, ventricular and hippocampal atrophy rates using the k-means boundary shift integral (BSI). Scan quality was visually assessed and the proportion of good quality accelerated and non-accelerated scans compared. We also compared MMSE scores, vascular burden and age between subjects with poor quality scans with those with good quality scans. Finally, we estimated sample size requirements for a hypothetical clinical trial when using atrophy rates from accelerated scans and non-accelerated scans. No significant differences in whole-brain, ventricular and hippocampal volumes and atrophy rates were found between accelerated and non-accelerated scans. Twice as many non-accelerated scan pairs suffered from at least some motion artefacts compared with accelerated scan pairs (p ≤ 0.001), which may influence the BSI. Subjects whose accelerated scans had significant motion had a higher mean vascular burden and age (p ≤ 0.05) whilst subjects whose non-accelerated scans had significant motion had poorer MMSE scores (p ≤ 0.05). No difference in estimated sample size requirements was found when using accelerated vs. non-accelerated scans. Accelerated scans reduce scan time and are better tolerated. Therefore it may be advantageous to use accelerated over non-accelerated scans in clinical trials that use ADNI-type protocols, especially in more cognitively impaired subjects.

  9. NIH Conference. Brain imaging: aging and dementia

    SciTech Connect

    Cutler, N.R.; Duara, R.; Creasey, H.; Grady, C.L.; Haxby, J.V.; Schapiro, M.B.; Rapoport, S.I.

    1984-09-01

    The brain imaging techniques of positron emission tomography using (18F)-fluoro-2-deoxy-D-glucose, and computed tomography, together with neuropsychological tests, were used to examine overall brain function and anatomy in three study populations: healthy men at different ages, patients with presumptive Alzheimer's disease, and adults with Down's syndrome. Brain glucose use did not differ with age, whereas an age-related decrement in gray matter volume was found on computed tomographic assessment in healthy subjects. Memory deficits were found to precede significant reductions in brain glucose utilization in mild to moderate Alzheimer's dementia. Furthermore, differences between language and visuoconstructive impairments in patients with mild to moderate Alzheimer's disease were related to hemispheric asymmetry of brain metabolism. Brain glucose utilization was found to be significantly elevated in young adults with Down's syndrome, compared with controls. The importance of establishing strict criteria for selecting control subjects and patients is explained in relation to the findings.

  10. Are Anxiety Disorders Associated with Accelerated Aging? A Focus on Neuroprogression

    PubMed Central

    Perna, Giampaolo; Iannone, Giuseppe; Alciati, Alessandra; Caldirola, Daniela

    2016-01-01

    Anxiety disorders (AnxDs) are highly prevalent throughout the lifespan, with detrimental effects on daily-life functioning, somatic health, and quality of life. An emerging perspective suggested that AnxDs may be associated with accelerated aging. In this paper, we explored the association between AnxDs and hallmarks of accelerated aging, with a specific focus on neuroprogression. We reviewed animal and human findings that suggest an overlap between processes of impaired neurogenesis, neurodegeneration, structural, functional, molecular, and cellular modifications in AnxDs, and aging. Although this research is at an early stage, our review suggests a link between anxiety and accelerated aging across multiple processes involved in neuroprogression. Brain structural and functional changes that accompany normal aging were more pronounced in subjects with AnxDs than in coevals without AnxDs, including reduced grey matter density, white matter alterations, impaired functional connectivity of large-scale brain networks, and poorer cognitive performance. Similarly, molecular correlates of brain aging, including telomere shortening, Aβ accumulation, and immune-inflammatory and oxidative/nitrosative stress, were overrepresented in anxious subjects. No conclusions about causality or directionality between anxiety and accelerated aging can be drawn. Potential mechanisms of this association, limitations of the current research, and implications for treatments and future studies are discussed. PMID:26881136

  11. Cellular senescence and the aging brain

    PubMed Central

    Chinta, Shankar J.; Woods, Georgia; Rane, Anand; Demaria, Marco; Campisi, Judith; Andersen, Julie K

    2014-01-01

    Cellular senescence is a potent anti-cancer mechanism that arrests the proliferation of mitotically competent cells to prevent malignant transformation. Senescent cells accumulate with age in a variety of human and mouse tissues where they express a complex ‘senescence-associated secretory phenotype’ (SASP). The SASP includes many pro-inflammatory cytokines, chemokines, growth factors and proteases that have the potential to cause or exacerbate age-related pathology, both degenerative and hyperplastic. While cellular senescence in peripheral tissues has recently been linked to a number of age-related pathologies, its involvement in brain aging is just beginning to be explored. Recent data generated by several laboratories suggest both aging and age-related neurodegenerative diseases are accompanied by an increase in SASP-expressing senescent cells of non-neuronal origin in the brain. Moreover, this increase correlates with neurodegeneration. Senescent cells in the brain could therefore constitute novel therapeutic targets for treating age-related neuropathologies. PMID:25281806

  12. Predicting brain acceleration during heading of soccer ball

    NASA Astrophysics Data System (ADS)

    Taha, Zahari; Hasnun Arif Hassan, Mohd; Azri Aris, Mohd; Anuar, Zulfika

    2013-12-01

    There has been a long debate whether purposeful heading could cause harm to the brain. Studies have shown that repetitive heading could lead to degeneration of brain cells, which is similarly found in patients with mild traumatic brain injury. A two-degree of freedom linear mathematical model was developed to study the impact of soccer ball to the brain during ball-to-head impact in soccer. From the model, the acceleration of the brain upon impact can be obtained. The model is a mass-spring-damper system, in which the skull is modelled as a mass and the neck is modelled as a spring-damper system. The brain is a mass with suspension characteristics that are also defined by a spring and a damper. The model was validated by experiment, in which a ball was dropped from different heights onto an instrumented dummy skull. The validation shows that the results obtained from the model are in a good agreement with the brain acceleration measured from the experiment. This findings show that a simple linear mathematical model can be useful in giving a preliminary insight on what human brain endures during a ball-to-head impact.

  13. Structural Imaging Measures of Brain Aging

    PubMed Central

    Lockhart, Samuel N.

    2014-01-01

    During the course of normal aging, biological changes occur in the brain that are associated with changes in cognitive ability. This review presents data from neuroimaging studies of primarily “normal” or healthy brain aging. As such, we focus on research in unimpaired or nondemented older adults, but also include findings from lifespan studies that include younger and middle aged individuals as well as from populations with prodromal or clinically symptomatic disease such as cerebrovascular or Alzheimer’s disease. This review predominantly addresses structural MRI biomarkers, such as volumetric or thickness measures from anatomical images, and measures of white matter injury and integrity respectively from FLAIR or DTI, and includes complementary data from PET and cognitive or clinical testing as appropriate. The findings reveal highly consistent age-related differences in brain structure, particularly frontal lobe and medial temporal regions that are also accompanied by age-related differences in frontal and medial temporal lobe mediated cognitive abilities. Newer findings also suggest that degeneration of specific white matter tracts such as those passing through the genu and splenium of the corpus callosum may also be related to age-related differences in cognitive performance. Interpretation of these findings, however, must be tempered by the fact that comorbid diseases such as cerebrovascular and Alzheimer’s disease also increase in prevalence with advancing age. As such, this review discusses challenges related to interpretation of current theories of cognitive aging in light of the common occurrence of these later-life diseases. Understanding the differences between “Normal” and “Healthy” brain aging and identifying potential modifiable risk factors for brain aging is critical to inform potential treatments to stall or reverse the effects of brain aging and possibly extend cognitive health for our aging society. PMID:25146995

  14. Aging-associated changes in human brain.

    PubMed

    Mrak, R E; Griffin, S T; Graham, D I

    1997-12-01

    A wide variety of anatomic and histological alterations are common in brains of aged individuals. However, identification of intrinsic aging changes--as distinct from changes resulting from cumulative environmental insult--is problematic. Some degree of neuronal and volume loss would appear to be inevitable, but recent studies have suggested that the magnitudes of such changes are much less than previously thought, and studies of dendritic complexity in cognitively intact individuals suggest continuing neuronal plasticity into the eighth decade. A number of vascular changes become more frequent with age, many attributable to systemic conditions such as hypertension and atherosclerosis. Age-associated vascular changes not clearly linked to such conditions include hyaline arteriosclerotic changes with formation of arterial tortuosities in small intracranial vessels and the radiographic changes in deep cerebral white matter known as "leukoaraiosis." Aging is accompanied by increases in glial cell activation, in oxidative damage to proteins and lipids, in irreversible protein glycation, and in damage to DNA, and such changes may underlie in part the age-associated increasing incidence of "degenerative" conditions such as Alzheimer disease and Parkinson disease. A small number of histological changes appear to be universal in aged human brains. These include increasing numbers of corpora amylacea within astrocytic processes near blood-brain or cerebrospinal fluid-brain interfaces, accumulation of the "aging" pigment lipofuscin in all brain regions, and appearance of Alzheimer-type neurofibrillary tangles (but not necessarily amyloid plaques) in mesial temporal structures.

  15. Braking and Accelerating of the Adolescent Brain

    PubMed Central

    Casey, BJ; Jones, Rebecca M.; Somerville, Leah H.

    2011-01-01

    Adolescence is a developmental period often characterized as a time of impulsive and risky choices leading to increased incidence of unintentional injuries and violence, alcohol and drug abuse, unintended pregnancy and sexually transmitted diseases. Traditional neurobiological and cognitive explanations for such suboptimal choices and actions have failed to account for nonlinear changes in behavior observed during adolescence, relative to childhood and adulthood. This review provides a biologically plausible conceptualization of the mechanisms underlying these nonlinear changes in behavior, as an imbalance between a heightened sensitivity to motivational cues and immature cognitive control. Recent human imaging and animal studies provide a biological basis for this view, suggesting differential development of subcortical limbic systems relative to top-down control systems during adolescence relative to childhood and adulthood. This work emphasizes the importance of examining transitions into and out of adolescence and highlights emerging avenues of future research on adolescent brain development. PMID:21475613

  16. Predicting healthy older adult's brain age based on structural connectivity networks using artificial neural networks.

    PubMed

    Lin, Lan; Jin, Cong; Fu, Zhenrong; Zhang, Baiwen; Bin, Guangyu; Wu, Shuicai

    2016-03-01

    Brain ageing is followed by changes of the connectivity of white matter (WM) and changes of the grey matter (GM) concentration. Neurodegenerative disease is more vulnerable to an accelerated brain ageing, which is associated with prospective cognitive decline and disease severity. Accurate detection of accelerated ageing based on brain network analysis has a great potential for early interventions designed to hinder atypical brain changes. To capture the brain ageing, we proposed a novel computational approach for modeling the 112 normal older subjects (aged 50-79 years) brain age by connectivity analyses of networks of the brain. Our proposed method applied principal component analysis (PCA) to reduce the redundancy in network topological parameters. Back propagation artificial neural network (BPANN) improved by hybrid genetic algorithm (GA) and Levenberg-Marquardt (LM) algorithm is established to model the relation among principal components (PCs) and brain age. The predicted brain age is strongly correlated with chronological age (r=0.8). The model has mean absolute error (MAE) of 4.29 years. Therefore, we believe the method can provide a possible way to quantitatively describe the typical and atypical network organization of human brain and serve as a biomarker for presymptomatic detection of neurodegenerative diseases in the future.

  17. Accelerated Aging of the M119 Simulator

    NASA Technical Reports Server (NTRS)

    Bixon, Eric R.

    2000-01-01

    This paper addresses the storage requirement, shelf life, and the reliability of M119 Whistling Simulator. Experimental conditions have been determined and the data analysis has been completed for the accelerated testing of the system. A general methodology to evaluate the shelf life of the system as a function of the storage time, temperature, and relative humidity is discussed.

  18. Acceleration of the aging process by oxygen

    NASA Technical Reports Server (NTRS)

    Miquel, J.; Lunderen, P. R.; Bensch, K. G.

    1975-01-01

    Tissue changes induced by hyperoxia have been compared with those of normal aging. Results of investigations using male flies prompt conclusion that normal aging, radiation syndrome, and hyperoxic injury share at least one common feature--lipid peroxidation damage to all mambranes resulting in accumulation of age pigment.

  19. The coming acceleration of global population ageing.

    PubMed

    Lutz, Wolfgang; Sanderson, Warren; Scherbov, Sergei

    2008-02-07

    The future paths of population ageing result from specific combinations of declining fertility and increasing life expectancies in different parts of the world. Here we measure the speed of population ageing by using conventional measures and new ones that take changes in longevity into account for the world as a whole and for 13 major regions. We report on future levels of indicators of ageing and the speed at which they change. We show how these depend on whether changes in life expectancy are taken into account. We also show that the speed of ageing is likely to increase over the coming decades and to decelerate in most regions by mid-century. All our measures indicate a continuous ageing of the world's population throughout the century. The median age of the world's population increases from 26.6 years in 2000 to 37.3 years in 2050 and then to 45.6 years in 2100, when it is not adjusted for longevity increase. When increases in life expectancy are taken into account, the adjusted median age rises from 26.6 in 2000 to 31.1 in 2050 and only to 32.9 in 2100, slightly less than what it was in the China region in 2005. There are large differences in the regional patterns of ageing. In North America, the median age adjusted for life expectancy change falls throughout almost the entire century, whereas the conventional median age increases significantly. Our assessment of trends in ageing is based on new probabilistic population forecasts. The probability that growth in the world's population will end during this century is 88%, somewhat higher than previously assessed. After mid-century, lower rates of population growth are likely to coincide with slower rates of ageing.

  20. Apoptosis in the aged dog brain.

    PubMed

    Kiatipattanasakul, W; Nakamura, S; Hossain, M M; Nakayama, H; Uchino, T; Shumiya, S; Goto, N; Doi, K

    1996-09-01

    Apoptosis similar to that seen in Alzheimer's disease patients was found in the brain of aged dogs by the TUNEL method of detecting in situ DNA fragmentation. Apoptosis was observed in both neurons and glial cells, and was morphologically characterized by round and swollen cytoplasm and aggregated nuclear chromatin, although these changes were slight. Neurons and astrocytes in the gray matter and oligodendrocytes in the white matter were affected. The number of ApopTag-positive brain cells increased slightly with age, but was not correlated to the number of senile plaques. A good correlation between the number of ApopTag-positive cells and the dementia index was clearly found. The present study indicates that brain cell apoptosis could account for dementia in aged dogs and suggested that aged dogs may be useful as a simplified animal model for Alzheimer's disease in man.

  1. Metabolic drift in the aging brain

    PubMed Central

    Ivanisevic, Julijana; Stauch, Kelly L.; Petrascheck, Michael; Benton, H. Paul; Epstein, Adrian A.; Fang, Mingliang; Gorantla, Santhi; Tran, Minerva; Hoang, Linh; Kurczy, Michael E.; Boska, Michael D.; Gendelman, Howard E.; Fox, Howard S.; Siuzdak, Gary

    2016-01-01

    Brain function is highly dependent upon controlled energy metabolism whose loss heralds cognitive impairments. This is particularly notable in the aged individuals and in age-related neurodegenerative diseases. However, how metabolic homeostasis is disrupted in the aging brain is still poorly understood. Here we performed global, metabolomic and proteomic analyses across different anatomical regions of mouse brain at different stages of its adult lifespan. Interestingly, while severe proteomic imbalance was absent, global-untargeted metabolomics revealed an energy metabolic drift or significant imbalance in core metabolite levels in aged mouse brains. Metabolic imbalance was characterized by compromised cellular energy status (NAD decline, increased AMP/ATP, purine/pyrimidine accumulation) and significantly altered oxidative phosphorylation and nucleotide biosynthesis and degradation. The central energy metabolic drift suggests a failure of the cellular machinery to restore metabostasis (metabolite homeostasis) in the aged brain and therefore an inability to respond properly to external stimuli, likely driving the alterations in signaling activity and thus in neuronal function and communication. PMID:27182841

  2. Advanced BrainAGE in older adults with type 2 diabetes mellitus

    PubMed Central

    Franke, Katja; Gaser, Christian; Manor, Brad; Novak, Vera

    2013-01-01

    Aging alters brain structure and function and diabetes mellitus (DM) may accelerate this process. This study investigated the effects of type 2 DM on individual brain aging as well as the relationships between individual brain aging, risk factors, and functional measures. To differentiate a pattern of brain atrophy that deviates from normal brain aging, we used the novel BrainAGE approach, which determines the complex multidimensional aging pattern within the whole brain by applying established kernel regression methods to anatomical brain magnetic resonance images (MRI). The “Brain Age Gap Estimation” (BrainAGE) score was then calculated as the difference between chronological age and estimated brain age. 185 subjects (98 with type 2 DM) completed an MRI at 3Tesla, laboratory and clinical assessments. Twenty-five subjects (12 with type 2 DM) also completed a follow-up visit after 3.8 ± 1.5 years. The estimated brain age of DM subjects was 4.6 ± 7.2 years greater than their chronological age (p = 0.0001), whereas within the control group, estimated brain age was similar to chronological age. As compared to baseline, the average BrainAGE scores of DM subjects increased by 0.2 years per follow-up year (p = 0.034), whereas the BrainAGE scores of controls did not change between baseline and follow-up. At baseline, across all subjects, higher BrainAGE scores were associated with greater smoking and alcohol consumption, higher tumor necrosis factor alpha (TNFα) levels, lower verbal fluency scores and more severe deprepession. Within the DM group, higher BrainAGE scores were associated with longer diabetes duration (r = 0.31, p = 0.019) and increased fasting blood glucose levels (r = 0.34, p = 0.025). In conclusion, type 2 DM is independently associated with structural changes in the brain that reflect advanced aging. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of abnormal patterns of brain aging associated with type 2

  3. Light-sensitive brain pathways and aging.

    PubMed

    Daneault, V; Dumont, M; Massé, É; Vandewalle, G; Carrier, J

    2016-03-15

    Notwithstanding its effects on the classical visual system allowing image formation, light acts upon several non-image-forming (NIF) functions including body temperature, hormonal secretions, sleep-wake cycle, alertness, and cognitive performance. Studies have shown that NIF functions are maximally sensitive to blue wavelengths (460-480 nm), in comparison to longer light wavelengths. Higher blue light sensitivity has been reported for melatonin suppression, pupillary constriction, vigilance, and performance improvement but also for modulation of cognitive brain functions. Studies investigating acute stimulating effects of light on brain activity during the execution of cognitive tasks have suggested that brain activations progress from subcortical regions involved in alertness, such as the thalamus, the hypothalamus, and the brainstem, before reaching cortical regions associated with the ongoing task. In the course of aging, lower blue light sensitivity of some NIF functions has been reported. Here, we first describe neural pathways underlying effects of light on NIF functions and we discuss eye and cerebral mechanisms associated with aging which may affect NIF light sensitivity. Thereafter, we report results of investigations on pupillary constriction and cognitive brain sensitivity to light in the course of aging. Whereas the impact of light on cognitive brain responses appears to decrease substantially, pupillary constriction seems to remain more intact over the lifespan. Altogether, these results demonstrate that aging research should take into account the diversity of the pathways underlying the effects of light on specific NIF functions which may explain their differences in light sensitivity.

  4. Accelerated food source location in aging Drosophila.

    PubMed

    Egenriether, Sada M; Chow, Eileen S; Krauth, Nathalie; Giebultowicz, Jadwiga M

    2015-10-01

    Adequate energy stores are essential for survival, and sophisticated neuroendocrine mechanisms evolved to stimulate foraging in response to nutrient deprivation. Food search behavior is usually investigated in young animals, and it is not known how aging alters this behavior. To address this question in Drosophila melanogaster, we compared the ability to locate food by olfaction in young and old flies using a food-filled trap. As aging is associated with a decline in motor functions, learning, and memory, we expected that aged flies would take longer to enter the food trap than their young counterparts. Surprisingly, old flies located food with significantly shorter latency than young ones. Robust food search behavior was associated with significantly lower fat reserves and lower starvation resistance in old flies. Food-finding latency (FFL) was shortened in young wild-type flies that were starved until their fat was depleted but also in heterozygous chico mutants with reduced insulin receptor activity and higher fat deposits. Conversely, food trap entry was delayed in old flies with increased insulin signaling. Our results suggest that the difference in FFL between young and old flies is linked to age-dependent differences in metabolic status and may be mediated by reduced insulin signaling.

  5. Accelerated Aging with Electrical Overstress and Prognostics for Power MOSFETs

    NASA Technical Reports Server (NTRS)

    Saha, Sankalita; Celaya, Jose Ramon; Vashchenko, Vladislav; Mahiuddin, Shompa; Goebel, Kai F.

    2011-01-01

    Power electronics play an increasingly important role in energy applications as part of their power converter circuits. Understanding the behavior of these devices, especially their failure modes as they age with nominal usage or sudden fault development is critical in ensuring efficiency. In this paper, a prognostics based health management of power MOSFETs undergoing accelerated aging through electrical overstress at the gate area is presented. Details of the accelerated aging methodology, modeling of the degradation process of the device and prognostics algorithm for prediction of the future state of health of the device are presented. Experiments with multiple devices demonstrate the performance of the model and the prognostics algorithm as well as the scope of application. Index Terms Power MOSFET, accelerated aging, prognostics

  6. Genomic integrity and the ageing brain.

    PubMed

    Chow, Hei-man; Herrup, Karl

    2015-11-01

    DNA damage is correlated with and may drive the ageing process. Neurons in the brain are postmitotic and are excluded from many forms of DNA repair; therefore, neurons are vulnerable to various neurodegenerative diseases. The challenges facing the field are to understand how and when neuronal DNA damage accumulates, how this loss of genomic integrity might serve as a 'time keeper' of nerve cell ageing and why this process manifests itself as different diseases in different individuals.

  7. Two hands, one brain, and aging.

    PubMed

    Maes, Celine; Gooijers, Jolien; Orban de Xivry, Jean-Jacques; Swinnen, Stephan P; Boisgontier, Matthieu P

    2017-02-08

    Many activities of daily living require moving both hands in an organized manner in space and time. Therefore, understanding the impact of aging on bimanual coordination is essential for prolonging functional independence and well-being in older adults. Here we investigated the behavioral and neural determinants of bimanual coordination in aging. The studies surveyed in this review reveal that aging is associated with cortical hyper-activity (but also subcortical hypo-activity) during performance of bimanual tasks. In addition to changes in activation in local areas, the interaction between distributed brain areas also exhibits age-related effects, i.e., functional connectivity is increased in the resting brain as well as during task performance. The mechanisms and triggers underlying these functional activation and connectivity changes remain to be investigated. This requires further research investment into the detailed study of interactions between brain structure, function and connectivity. This will also provide the foundation for interventional research programs towards preservation of brain health and behavioral performance by maximizing neuroplasticity potential in older adults.

  8. BrainAGE in Mild Cognitive Impaired Patients: Predicting the Conversion to Alzheimer's Disease.

    PubMed

    Gaser, Christian; Franke, Katja; Klöppel, Stefan; Koutsouleris, Nikolaos; Sauer, Heinrich

    2013-01-01

    Alzheimer's disease (AD), the most common form of dementia, shares many aspects of abnormal brain aging. We present a novel magnetic resonance imaging (MRI)-based biomarker that predicts the individual progression of mild cognitive impairment (MCI) to AD on the basis of pathological brain aging patterns. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE) score indicates accelerated atrophy and is considered a risk factor for conversion to AD. Here, the BrainAGE framework was applied to predict the individual brain ages of 195 subjects with MCI at baseline, of which a total of 133 developed AD during 36 months of follow-up (corresponding to a pre-test probability of 68%). The ability of the BrainAGE framework to correctly identify MCI-converters was compared with the performance of commonly used cognitive scales, hippocampus volume, and state-of-the-art biomarkers derived from cerebrospinal fluid (CSF). With accuracy rates of up to 81%, BrainAGE outperformed all cognitive scales and CSF biomarkers in predicting conversion of MCI to AD within 3 years of follow-up. Each additional year in the BrainAGE score was associated with a 10% greater risk of developing AD (hazard rate: 1.10 [CI: 1.07-1.13]). Furthermore, the post-test probability was increased to 90% when using baseline BrainAGE scores to predict conversion to AD. The presented framework allows an accurate prediction even with multicenter data. Its fast and fully automated nature facilitates the integration into the clinical workflow. It can be exploited as a tool for screening as well as for monitoring treatment options.

  9. BrainAGE in Mild Cognitive Impaired Patients: Predicting the Conversion to Alzheimer’s Disease

    PubMed Central

    Klöppel, Stefan; Koutsouleris, Nikolaos; Sauer, Heinrich

    2013-01-01

    Alzheimer’s disease (AD), the most common form of dementia, shares many aspects of abnormal brain aging. We present a novel magnetic resonance imaging (MRI)-based biomarker that predicts the individual progression of mild cognitive impairment (MCI) to AD on the basis of pathological brain aging patterns. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE) score indicates accelerated atrophy and is considered a risk factor for conversion to AD. Here, the BrainAGE framework was applied to predict the individual brain ages of 195 subjects with MCI at baseline, of which a total of 133 developed AD during 36 months of follow-up (corresponding to a pre-test probability of 68%). The ability of the BrainAGE framework to correctly identify MCI-converters was compared with the performance of commonly used cognitive scales, hippocampus volume, and state-of-the-art biomarkers derived from cerebrospinal fluid (CSF). With accuracy rates of up to 81%, BrainAGE outperformed all cognitive scales and CSF biomarkers in predicting conversion of MCI to AD within 3 years of follow-up. Each additional year in the BrainAGE score was associated with a 10% greater risk of developing AD (hazard rate: 1.10 [CI: 1.07–1.13]). Furthermore, the post-test probability was increased to 90% when using baseline BrainAGE scores to predict conversion to AD. The presented framework allows an accurate prediction even with multicenter data. Its fast and fully automated nature facilitates the integration into the clinical workflow. It can be exploited as a tool for screening as well as for monitoring treatment options. PMID:23826273

  10. Brain metabolism and blood flow during aging.

    PubMed

    Horwitz, B

    1987-01-01

    Recent studies of cerebral metabolism have suggested that although cerebral blood flow is reduced during rest in the healthy aged brain, there is little or no decline in resting glucose consumption. Intercorrelations between resting regional cerebral rates for glucose (rCMRglc), as determined by positron emission tomography using [18F]fluorodeoxyglucose, were shown to provide a measure of the functional associativity of brain regions. Partial correlation coefficients, controlling for whole brain glucose metabolism, were used in the analysis. Dividing the brain into 59 regions, we found, for 40 healthy males (21-83 years in age) in a state of reduced sensory input, that the strongest correlations generally were between bilaterally symmetric brain regions, and that there were many statistically significant correlations (P less than 0.01) among frontal and parietal lobe regions and also among temporal and occipital lobe areas, but few significant correlations between these two domains. The correlation analysis then was applied to two groups (15 healthy males each) of young (20-32 years old) and elderly (64-83 years old) subjects in the same resting state. Compared with the young group, we found that the elderly subjects have fewer statistically significant (P less than 0.01) correlations, with the most noteworthy reductions being between parietal and frontal lobe regions, and among parietal lobe areas. These findings indicated that cerebral functional interactions were reduced in the healthy elderly. The same analysis, applied to 21 mainly mildly-to-moderately impaired presumed Alzheimer subjects (and 21 age-matched controls), revealed fewer significant correlations between homologous brain regions which correspond to metabolic asymmetries linked to neuropsychological deficiencies.

  11. Gender-specific impact of personal health parameters on individual brain aging in cognitively unimpaired elderly subjects

    PubMed Central

    Franke, Katja; Ristow, Michael; Gaser, Christian

    2014-01-01

    Aging alters brain structure and function. Personal health markers and modifiable lifestyle factors are related to individual brain aging as well as to the risk of developing Alzheimer's disease (AD). This study used a novel magnetic resonance imaging (MRI)-based biomarker to assess the effects of 17 health markers on individual brain aging in cognitively unimpaired elderly subjects. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE) score indicates accelerated atrophy and is considered a risk factor for developing AD. Within this cross-sectional, multi-center study 228 cognitively unimpaired elderly subjects (118 males) completed an MRI at 1.5Tesla, physiological and blood parameter assessments. The multivariate regression model combining all measured parameters was capable of explaining 39% of BrainAGE variance in males (p < 0.001) and 32% in females (p < 0.01). Furthermore, markers of the metabolic syndrome as well as markers of liver and kidney functions were profoundly related to BrainAGE scores in males (p < 0.05). In females, markers of liver and kidney functions as well as supply of vitamin B12 were significantly related to BrainAGE (p < 0.05). In conclusion, in cognitively unimpaired elderly subjects several clinical markers of poor health were associated with subtle structural changes in the brain that reflect accelerated aging, whereas protective effects on brain aging were observed for markers of good health. Additionally, the relations between individual brain aging and miscellaneous health markers show gender-specific patterns. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of subtly abnormal patterns of brain aging probably preceding cognitive decline and development of AD. PMID:24904408

  12. Brain pathologies in extreme old age

    PubMed Central

    Neltner, Janna H.; Abner, Erin L.; Jicha, Gregory A.; Schmitt, Frederick A.; Patel, Ela; Poon, Leonard W.; Gearing, Marla; Green, Robert C.; Davey, Adam; Johnson, Mary Ann; Jazwinski, S. Michal; Kim, Sangkyu; Davis, Daron; Woodard, John L.; Kryscio, Richard J.; Van Eldik, Linda J.; Nelson, Peter T.

    2015-01-01

    With an emphasis on evolving concepts in the field, we evaluated neuropathologic data from very old research volunteers whose brain autopsies were performed at University of Kentucky (UK-ADC), incorporating data from the Georgia Centenarian Study (N=49 cases included), the Nun Study (N=17), and UK-ADC (N=11) cohorts. Average age of death was 102.0 years (range: 98–107) overall. Alzheimer’s disease (AD) pathology was not universal (62% with “moderate” or “frequent” neuritic amyloid plaque densities) whereas frontotemporal lobar degeneration (FTLD) was absent. By contrast, some hippocampal neurofibrillary tangles (including primary age-related tauopathy [PART]) were observed in every case. Lewy body pathology was seen in 16.9% of subjects, hippocampal sclerosis of aging (HS-Aging) in 20.8%. We describe anatomical distributions of pigment-laden macrophages, expanded Virchow-Robin spaces, and arteriolosclerosis among Georgia Centenarians. Moderate or severe arteriolosclerosis pathology, throughout the brain, was associated with both HS-Aging pathology and an ABCC9 gene variant. These results provide fresh insights into the complex cerebral multimorbidity, and a novel genetic risk factor, at the far end of the human aging spectrum. PMID:26597697

  13. Of sound mind and body: depression, disease, and accelerated aging

    PubMed Central

    M. Wolkowitz, Owen; I. Reus, Victor; H. Mellon, Synthia

    2011-01-01

    Major depressive disorder (MDD) is associated with a high rate of developing serious medical comorbidities such as cardiovascular disease, stroke, dementia, osteoporosis, diabetes, and the metabolic syndrome. These are conditions that typically occur late in life, and it has been suggested that MDD may be associated with “accelerated aging.” We review several moderators and mediators that may accompany MDD and that may give rise to these comorbid medical conditions. We first review the moderating effects of psychological styles of coping, genetic predisposition, and epigenetic modifications (eg, secondary to childhood adversity). We then focus on several interlinked mediators occurring in MDD (or at least in subtypes of MDD) that may contribute to the medical comorbidity burden and to accelerated aging: limbic-hypothalamic-pituitary-adrenal axis alterations, diminution in glucocorticoid receptor function, altered glucose tolerance and insulin sensitivity, excitotoxicity, increases in intracellular calcium, oxidative stress, a proinflammatory milieu, lowered levels of “counter-regulatory” neurosteroids (such as allopregnanolone and dehydroepiandrosterone), diminished neurotrophic activity, and accelerated cell aging, manifest as alterations in telomerase activity and as shortening of telomeres, which can lead to apoptosis and cell death. In this model, MDD is characterized by a surfeit of potentially destructive mediators and an insufficiency of protective or restorative ones. These factors interact in increasing the likelihood of physical disease and of accelerated aging at the cellular level. We conclude with suggestions for novel mechanism-based therapeutics based on these mediators. PMID:21485744

  14. [The accelerated aging of the population in Brazil].

    PubMed

    Cassab, Amanda Kampa

    2013-01-01

    Formerly a young country, Brazil is now undergoing a period of acceleration in the ageing of its population. The Brazilian geriatric heathcare sector must prepare itself to advocate and optimise the care of elderly patients. The training of professionals in gerontology must be a priority and public policies need to evolve.

  15. Accelerated aging-related transcriptome changes in the female prefrontal cortex.

    PubMed

    Yuan, Yuan; Chen, Yi-Ping Phoebe; Boyd-Kirkup, Jerome; Khaitovich, Philipp; Somel, Mehmet

    2012-10-01

    Human female life expectancy is higher than that of males. Intriguingly, it has been reported that women display faster rates of age-related cognitive decline and a higher prevalence of Alzheimer's disease (AD). To assess the molecular bases of these contradictory trends, we analyzed differences in expression changes with age between adult males and females, in four brain regions. In the superior frontal gyrus (SFG), a part of the prefrontal cortex, we observed manifest differences between the two sexes in the timing of age-related changes, that is, sexual heterochrony. Intriguingly, age-related expression changes predominantly occurred earlier, or at a faster pace, in females compared to men. These changes included decreased energy production and neural function and up-regulation of the immune response, all major features of brain aging. Furthermore, we found that accelerated expression changes in the female SFG correlated with expression changes observed in AD, as well as stress effects in the frontal cortex. Accelerated aging-related changes in the female SFG transcriptome may provide a link between a higher stress exposure or sensitivity in women and the higher prevalence of AD.

  16. Accelerated aging of GaAs concentrator solar cells

    SciTech Connect

    Gregory, P.E.

    1982-04-01

    An accelerated aging study of AlGaAs/GaAs solar cells has been completed. The purpose of the study was to identify the possible degradation mechanisms of AlGaAs/GaAs solar cells in terrestrial applications. Thermal storage tests and accelerated AlGaAs corrosion studies were performed to provide an experimental basis for a statistical analysis of the estimated lifetime. Results of this study suggest that a properly designed and fabricated AlGaAs/GaAs solar cell can be mechanically rugged and environmentally stable with projected lifetimes exceeding 100 years.

  17. The emotion paradox in the aging brain

    PubMed Central

    Mather, Mara

    2012-01-01

    This paper reviews age differences in emotion processing and how they may relate to age-related changes in the brain. Compared with younger adults, older adults react less to negative situations, ignore irrelevant negative stimuli better, and remember relatively more positive than negative information. Older adults’ ability to insulate their thoughts and emotional reactions from negative situations is likely due to a number of factors, such as being less influenced by interoceptive cues, selecting different emotion regulation strategies, having less age-related decline in prefrontal regions associated with emotional control than in other prefrontal regions, and engaging in emotion regulation strategies as a default mode in their everyday lives. Healthy older adults’ avoidance of processing negative stimuli may contribute to their well-maintained emotional well-being. However, when cardiovascular disease leads to additional prefrontal white matter damage, older adults have fewer cognitive control mechanisms available to regulate their emotions, making them more vulnerable to depression. In general, while age-related changes in the brain help shape emotional experience, shifts in preferred strategies and goal priorities are also important influences. PMID:22409159

  18. Accelerated aging test results for aerospace wire insulation constructions

    NASA Technical Reports Server (NTRS)

    Dunbar, William G.

    1995-01-01

    Several wire insulation constructions were evaluated with and without continuous glow discharges at low pressure and high temperature to determine the aging characteristics of acceptable wire insulation constructions. It was known at the beginning of the test program that insulation aging takes several years when operated at normal ambient temperature and pressure of 20 C and 760 torr. Likewise, it was known that the accelerated aging process decreases insulation life by approximately 50% for each 10 C temperature rise. Therefore, the first phases of the program, not reported in these test results, were to select wire insulation constructions that could operate at high temperature and low pressure for over 10,000 hours with negligible shrinkage and little materials' deterioration.The final phase of the program was to determine accelerated aging characteristics. When an insulation construction is subjected to partial discharges the insulation is locally heated by the bombardment of the discharges, the insulation is also subjected to ozone and other deteriorating gas particles that may significantly increase the aging process. Several insulation systems using either a single material or combinations of teflon, kapton, and glass insulation constructions were tested. All constructions were rated to be partial discharge and/or corona-free at 240 volts, 400 Hz and 260 C (500 F) for 50, 000 hours at altitudes equivalent to the Paschen law. Minimum partial discharge aging tests were preceded by screening tests lasting 20 hours at 260 C. The aging process was accelerated by subjecting the test articles to temperatures up to 370 C (700 F) with and without partial discharges. After one month operation with continuous glow discharges surrounding the test articles, most insulation systems were either destroyed or became brittle, cracked, and unsafe for use. Time with space radiation as with partial discharges is accumulative.

  19. Progranulin Knockout Accelerates Intervertebral Disc Degeneration in Aging Mice

    PubMed Central

    Zhao, Yun-peng; Tian, Qing-yun; Liu, Ben; Cuellar, Jason; Richbourgh, Brendon; Jia, Tang-hong; Liu, Chuan-ju

    2015-01-01

    Intervertebral disc (IVD) degeneration is a common degenerative disease, yet much is unknown about the mechanisms during its pathogenesis. Herein we investigated whether progranulin (PGRN), a chondroprotective growth factor, is associated with IVD degeneration. PGRN was detectable in both human and murine IVD. The levels of PGRN were upregulated in murine IVD tissue during aging process. Loss of PGRN resulted in an early onset of degenerative changes in the IVD tissue and altered expressions of the degeneration-associated molecules in the mouse IVD tissue. Moreover, PGRN knockout mice exhibited accelerated IVD matrix degeneration, abnormal bone formation and exaggerated bone resorption in vertebra with aging. The acceleration of IVD degeneration observed in PGRN null mice was probably due to the enhanced activation of NF-κB signaling and β-catenin signaling. Taken together, PGRN may play a critical role in homeostasis of IVD, and may serve as a potential molecular target for prevention and treatment of disc degenerative diseases. PMID:25777988

  20. Harvard Aging Brain Study: Dataset and accessibility.

    PubMed

    Dagley, Alexander; LaPoint, Molly; Huijbers, Willem; Hedden, Trey; McLaren, Donald G; Chatwal, Jasmeer P; Papp, Kathryn V; Amariglio, Rebecca E; Blacker, Deborah; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Schultz, Aaron P

    2017-01-01

    The Harvard Aging Brain Study is sharing its data with the global research community. The longitudinal dataset consists of a 284-subject cohort with the following modalities acquired: demographics, clinical assessment, comprehensive neuropsychological testing, clinical biomarkers, and neuroimaging. To promote more extensive analyses, imaging data was designed to be compatible with other publicly available datasets. A cloud-based system enables access to interested researchers with blinded data available contingent upon completion of a data usage agreement and administrative approval. Data collection is ongoing and currently in its fifth year.

  1. Mechanisms of aging in senescence-accelerated mice

    PubMed Central

    Carter, Todd A; Greenhall, Jennifer A; Yoshida, Shigeo; Fuchs, Sebastian; Helton, Robert; Swaroop, Anand; Lockhart, David J; Barlow, Carrolee

    2005-01-01

    Background Progressive neurological dysfunction is a key aspect of human aging. Because of underlying differences in the aging of mice and humans, useful mouse models have been difficult to obtain and study. We have used gene-expression analysis and polymorphism screening to study molecular senescence of the retina and hippocampus in two rare inbred mouse models of accelerated neurological senescence (SAMP8 and SAMP10) that closely mimic human neurological aging, and in a related normal strain (SAMR1) and an unrelated normal strain (C57BL/6J). Results The majority of age-related gene expression changes were strain-specific, with only a few common pathways found for normal and accelerated neurological aging. Polymorphism screening led to the identification of mutations that could have a direct impact on important disease processes, including a mutation in a fibroblast growth factor gene, Fgf1, and a mutation in and ectopic expression of the gene for the chemokine CCL19, which is involved in the inflammatory response. Conclusion We show that combining the study of inbred mouse strains with interesting traits and gene-expression profiling can lead to the discovery of genes important for complex phenotypes. Furthermore, full-genome polymorphism detection, sequencing and gene-expression profiling of inbred mouse strains with interesting phenotypic differences may provide unique insights into the molecular genetics of late-manifesting complex diseases. PMID:15960800

  2. Tracking accelerated aging of composites with ultrasonic attenuation measurements

    SciTech Connect

    Chinn, D.J.; Durbin, P.F.; Thomas, G.H.; Groves, S.E.

    1996-10-01

    Composite materials are steadily replacing traditional materials in many industries. For many carbon composite materials, particularly in aerospace applications, durability is a critical design parameter which must be accurately characterized. Lawrence Livermore National Laboratory (LLNL) and Boeing Commercial Airplane Group have established a cooperative research and development agreement (CRADA) to assist in the high speed research program at Boeing. LLNL`s expertise in fiber composites, computer modeling, mechanical testing, chemical analysis and nondestructive evaluation (ND) will contribute to the study of advanced composite materials in commercial aerospace applications. Through thermo-mechanical experiments with periodic chemical analysis and nondestructive evaluation, the aging mechanisms in several continuous fiber polymer composites will be studied. Several measurement techniques are being studied for their correlation with aging. This paper describes through-transmission ultrasonic attenuation measurements of isothermally aged composite materials and their use as a tracking parameter for accelerated aging.

  3. A common brain network links development, aging, and vulnerability to disease.

    PubMed

    Douaud, Gwenaëlle; Groves, Adrian R; Tamnes, Christian K; Westlye, Lars Tjelta; Duff, Eugene P; Engvig, Andreas; Walhovd, Kristine B; James, Anthony; Gass, Achim; Monsch, Andreas U; Matthews, Paul M; Fjell, Anders M; Smith, Stephen M; Johansen-Berg, Heidi

    2014-12-09

    Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

  4. Effects of changing from non-accelerated to accelerated MRI for follow-up in brain atrophy measurement.

    PubMed

    Leung, Kelvin K; Malone, Ian M; Ourselin, Sebastien; Gunter, Jeffrey L; Bernstein, Matt A; Thompson, Paul M; Jack, Clifford R; Weiner, Michael W; Fox, Nick C

    2015-02-15

    Stable MR acquisition is essential for reliable measurement of brain atrophy in longitudinal studies. One attractive recent advance in MRI is to speed up acquisition using parallel imaging (e.g. reducing volumetric T1-weighted acquisition scan times from around 9 to 5 min). In some studies, a decision to change to an accelerated acquisition may have been deliberately taken, while in others repeat scans may occasionally be accidentally acquired with an accelerated acquisition. In ADNI, non-accelerated and accelerated scans were acquired in the same scanning session on each individual. We investigated the impact on brain atrophy as measured by k-means normalized boundary shift integral (KN-BSI) and deformation-based morphometry when changing from non-accelerated to accelerated MRI acquisitions over a 12-month interval using scans of 422 subjects from ADNI. KN-BSIs were calculated using both a non-accelerated baseline scan and non-accelerated 12-month scans (i.e. consistent acquisition), and a non-accelerated baseline scan and an accelerated 12-month scan (i.e. changed acquisition). Fluid-based non-rigid registration was also performed on those scans to estimate the brain atrophy rate. We found that the effect on KN-BSI and fluid-based non-rigid registration depended on the scanner manufacturer. For KN-BSI, in Philips and Siemens scanners, the change had very little impact on the measured atrophy rate (increase of 0.051% in Philips and -0.035% in Siemens from consistent acquisition to changed acquisition), whereas, in GE, the change caused a mean reduction of 0.65% in the brain atrophy rate. This is likely due to the difference in tissue contrast between gray matter and cerebrospinal fluid in the non-accelerated and accelerated scans in GE, which uses IR-FSPGR instead of MP-RAGE. For fluid-based non-rigid registration, the change caused a mean increase of 0.29% in the brain atrophy rate in the changed acquisition compared with consistent acquisition in Philips

  5. Electrochemical migration technique to accelerate ageing of cementitious materials

    NASA Astrophysics Data System (ADS)

    Babaahmadi, A.; Tang, L.; Abbas, Z.

    2013-07-01

    Durability assessment of concrete structures for constructions in nuclear waste repositories requires long term service life predictions. As deposition of low and intermediate level radioactive waste (LILW) takes up to 100 000 years, it is necessary to analyze the service life of cementitious materials in this time perspective. Using acceleration methods producing aged specimens would decrease the need of extrapolating short term data sets. Laboratory methods are therefore, needed for accelerating the ageing process without making any influencing distortion in the properties of the materials. This paper presents an electro-chemical migration method to increase the rate of calcium leaching from cementitious specimens. This method is developed based on the fact that major long term deterioration process of hardened cement paste in concrete structures for deposition of LILW is due to slow diffusion of calcium ions. In this method the cementitious specimen is placed in an electrochemical cell as a porous path way through which ions can migrate at a rate far higher than diffusion process. The electrical field is applied to the cell in a way to accelerate the ion migration without making destructions in the specimen's micro and macroscopic properties. The anolyte and catholyte solutions are designed favoring dissolution of calcium hydroxide and compensating for the leached calcium ions with another ion like lithium.

  6. Shelf life determination of an epoxy resin by accelerated aging

    SciTech Connect

    Smith, H.M.

    1983-11-01

    The objectives of the study reported were to first define the rate and mode of degradation of an epoxy resin at two storage conditions, 4.4/sup 0/C and 25/sup 0/C, by means of a thermally accelerated aging experiment. Then, samples which had been aged the equivalent of at least 10 years at each storage condition would be tested for conformance to the material specifications. The study's results demonstrate that the commercial resin could be acquired and stored for the required 10 to 11 years without concern over degradation. The expected changes at the two storage temperatures have been defined. Aged resin samples are shown to yield an acceptable product. Sufficient data exist to predict the changes in viscosity and epoxide equivalent of the resin at any other storage temperature of interest. (LEW)

  7. Cerebrolysin Accelerates Metamorphosis and Attenuates Aging-Accelerating Effect of High Temperature in Drosophila Melanogaster

    PubMed Central

    Navrotskaya, V.; Vorobyova, L.; Sharma, H.; Muresanu, D.; Summergrad, P.

    2015-01-01

    Cerebrolysin® (CBL) is a neuroprotective drug used for the treatment of neurodegenerative diseases. CBL’s mechanisms of action remain unclear. Involvement of tryptophan (TRP)–kynurenine (KYN) pathway in neuroprotective effect of CBL might be suggested considering that modulation of KYN pathway of TRP metabolism by CBL, and protection against eclosion defect and prolongation of life span of Drosophila melanogaster with pharmacologically or genetically-induced down-regulation of TRP conversion into KYN. To investigate possible involvement of TRP–KYN pathway in mechanisms of neuroprotective effect of CBL, we evaluated CBL effects on metamorphosis and life span of Drosophila melanogaster maintained at 23 °C and 28 °C ambient temperature. CBL accelerated metamorphosis, exerted strong tendency (p = 0.04) to prolong life span in female but not in male flies, and attenuated aging-accelerating effect of high (28 °C) ambient temperature in both female and male flies. Further research of CBL effects on metamorphosis and resistance to aging-accelerating effect of high temperature might offer new insights in mechanisms of its neuroprotective action and expand its clinical applications. PMID:25798213

  8. Social support, stress and the aging brain.

    PubMed

    Sherman, Stephanie M; Cheng, Yen-Pi; Fingerman, Karen L; Schnyer, David M

    2016-07-01

    Social support benefits health and well-being in older individuals, however the mechanism remains poorly understood. One proposal, the stress-buffering hypothesis states social support 'buffers' the effects of stress on health. Alternatively, the main effect hypothesis suggests social support independently promotes health. We examined the combined association of social support and stress on the aging brain. Forty healthy older adults completed stress questionnaires, a social network interview and structural MRI to investigate the amygdala-medial prefrontal cortex circuitry, which is implicated in social and emotional processing and negatively affected by stress. Social support was positively correlated with right medial prefrontal cortical thickness while amygdala volume was negatively associated with social support and positively related to stress. We examined whether the association between social support and amygdala volume varied across stress level. Stress and social support uniquely contribute to amygdala volume, which is consistent with the health benefits of social support being independent of stress.

  9. Accelerated Aging Experiments for Capacitor Health Monitoring and Prognostics

    NASA Technical Reports Server (NTRS)

    Kulkarni, Chetan S.; Celaya, Jose Ramon; Biswas, Gautam; Goebel, Kai

    2012-01-01

    This paper discusses experimental setups for health monitoring and prognostics of electrolytic capacitors under nominal operation and accelerated aging conditions. Electrolytic capacitors have higher failure rates than other components in electronic systems like power drives, power converters etc. Our current work focuses on developing first-principles-based degradation models for electrolytic capacitors under varying electrical and thermal stress conditions. Prognostics and health management for electronic systems aims to predict the onset of faults, study causes for system degradation, and accurately compute remaining useful life. Accelerated life test methods are often used in prognostics research as a way to model multiple causes and assess the effects of the degradation process through time. It also allows for the identification and study of different failure mechanisms and their relationships under different operating conditions. Experiments are designed for aging of the capacitors such that the degradation pattern induced by the aging can be monitored and analyzed. Experimental setups and data collection methods are presented to demonstrate this approach.

  10. The Influence of the Brain on Overpopulation, Ageing and Dependency.

    ERIC Educational Resources Information Center

    Cape, Ronald D. T.

    1989-01-01

    With time, an increasing number in the world population is becoming old, and changes in the aging brain mean that a significant proportion of the aged are likely to be dependent on others. The devotion of resources to research into the aging brain could bring benefits far outweighing the investment. (Author/CW)

  11. Accelerated Aging Influences Cardiovascular Disease Risk in Rheumatoid Arthritis

    PubMed Central

    Crowson, Cynthia S.; Therneau, Terry M.; Davis, John M.; Roger, Véronique L.; Matteson, Eric L.; Gabriel, Sherine E.

    2014-01-01

    OBJECTIVE To determine whether the impact of aging on cardiovascular disease (CVD) risk in the general population (as estimated by the Framingham risk score [FRS]) differs in patients with rheumatoid arthritis (RA). METHODS A population-based inception cohort of Olmsted County, Minnesota residents aged ≥30 years who fulfilled 1987 ACR criteria for RA in 1988–2008 was assembled and followed until death, migration, or 7-1-2012. Data on CVD events were collected by medical record review. The 10-year FRS for CVD was calculated. Cox models adjusted for FRS were used to examine the influence of age on CVD risk. RESULTS The study included 563 patients with RA without prior CVD (mean age: 55 years, 72% women; 69% seropositive [i.e., rheumatoid factor and/or anti-citrullinated protein antibody positive]). During a mean follow-up of 8.2 years, 98 patients developed CVD (74 seropositive and 24 seronegative), but FRS predicted only 59.7 events (35.4 seropositive and 24.3 seronegative). The gap between observed and predicted CVD risk increased exponentially across age, and the age effect on CVD risk in seropositive RA was nearly double its effect in the general population with additional log(age) coefficients of 2.91 for women (p=0.002) and 2.06 for men (p=0.027). CONCLUSION Age exerts an exponentially increasing effect on CVD risk in seropositive RA, but no increased effect among seronegative patients. The causes of accelerated aging in patients with seropositive RA deserve further investigation. PMID:23818136

  12. Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function.

    PubMed

    Baruch, Kuti; Deczkowska, Aleksandra; David, Eyal; Castellano, Joseph M; Miller, Omer; Kertser, Alexander; Berkutzki, Tamara; Barnett-Itzhaki, Zohar; Bezalel, Dana; Wyss-Coray, Tony; Amit, Ido; Schwartz, Michal

    2014-10-03

    Aging-associated cognitive decline is affected by factors produced inside and outside the brain. By using multiorgan genome-wide analysis of aged mice, we found that the choroid plexus, an interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent gene expression profile that was also found in aged human brains. In aged mice, this response was induced by brain-derived signals, present in the cerebrospinal fluid. Blocking IFN-I signaling within the aged brain partially restored cognitive function and hippocampal neurogenesis and reestablished IFN-II-dependent choroid plexus activity, which is lost in aging. Our data identify a chronic aging-induced IFN-I signature, often associated with antiviral response, at the brain's choroid plexus and demonstrate its negative influence on brain function, thereby suggesting a target for ameliorating cognitive decline in aging.

  13. Parasite infection accelerates age polyethism in young honey bees.

    PubMed

    Lecocq, Antoine; Jensen, Annette Bruun; Kryger, Per; Nieh, James C

    2016-02-25

    Honey bees (Apis mellifera) are important pollinators and their health is threatened worldwide by persistent exposure to a wide range of factors including pesticides, poor nutrition, and pathogens. Nosema ceranae is a ubiquitous microsporidian associated with high colony mortality. We used lab micro-colonies of honey bees and video analyses to track the effects of N. ceranae infection and exposure on a range of individual and social behaviours in young adult bees. We provide detailed data showing that N. ceranae infection significantly accelerated the age polyethism of young bees, causing them to exhibit behaviours typical of older bees. Bees with high N. ceranae spore counts had significantly increased walking rates and decreased attraction to queen mandibular pheromone. Infected bees also exhibited higher rates of trophallaxis (food exchange), potentially reflecting parasite manipulation to increase colony infection. However, reduction in queen contacts could help bees limit the spread of infection. Such accelerated age polyethism may provide a form of behavioural immunity, particularly if it is elicited by a wide variety of pathogens.

  14. Parasite infection accelerates age polyethism in young honey bees

    PubMed Central

    Lecocq, Antoine; Jensen, Annette Bruun; Kryger, Per; Nieh, James C.

    2016-01-01

    Honey bees (Apis mellifera) are important pollinators and their health is threatened worldwide by persistent exposure to a wide range of factors including pesticides, poor nutrition, and pathogens. Nosema ceranae is a ubiquitous microsporidian associated with high colony mortality. We used lab micro-colonies of honey bees and video analyses to track the effects of N. ceranae infection and exposure on a range of individual and social behaviours in young adult bees. We provide detailed data showing that N. ceranae infection significantly accelerated the age polyethism of young bees, causing them to exhibit behaviours typical of older bees. Bees with high N. ceranae spore counts had significantly increased walking rates and decreased attraction to queen mandibular pheromone. Infected bees also exhibited higher rates of trophallaxis (food exchange), potentially reflecting parasite manipulation to increase colony infection. However, reduction in queen contacts could help bees limit the spread of infection. Such accelerated age polyethism may provide a form of behavioural immunity, particularly if it is elicited by a wide variety of pathogens. PMID:26912310

  15. Cardiorespiratory Fitness and Accelerated Cognitive Decline With Aging

    PubMed Central

    2014-01-01

    Background. Growing evidence suggests that self-reported physical activity accounts for variability in cognitive function among older adults, and aerobic intervention may improve cognitive function in this population. However, much less is known about the longitudinal association between direct measures of cardiorespiratory fitness and cognitive function across the life span. The present study examined the prospective association between symptom-limited maximal oxygen consumption (VO2max) and longitudinal performance on a comprehensive neuropsychological battery. Methods. Up to 1,400 participants aged 19–94 years underwent initial VO2max assessment and completed subsequent tests of memory, attention, perceptuomotor speed, language, and executive function, in addition to cognitive screening measures, on up to six occasions (mean, M = 2; standard deviation, SD = 1) for up to 18 years (M = 7, SD = 3). Mixed-effects regression models were adjusted for demographic, biomedical, and behavioral confounders. Results. Analyses revealed significant longitudinal associations between baseline VO2max and trajectory of performance on multiple measures of verbal and visual memory, as well as on a cognitive screening test (all ps < .05). Individuals with lower VO2max demonstrated accelerated trajectories of cognitive decline over time. Conclusions. Baseline cardiorespiratory fitness is related to longitudinal neuropsychological performance, and memory appears to be a particularly vulnerable domain. Evidence that aerobic fitness is associated with accelerated cognitive decline emphasizes the possible importance of behavioral interventions to optimize cognitive aging over time. PMID:24192540

  16. Dietary resistant starch improves selected brain and behavioral functions in adult and aged rodents.

    PubMed

    Zhou, June; Keenan, Michael J; Fernandez-Kim, Sun Ok; Pistell, Paul J; Ingram, Donald K; Li, Bing; Raggio, Anne M; Shen, Li; Zhang, Hanjie; McCutcheon, Kathleen L; Tulley, Richard T; Blackman, Marc R; Keller, Jeffrey N; Martin, Roy J

    2013-11-01

    Resistant starch (RS) is a dietary fiber that exerts multiple beneficial effects. The current study explored the effects of dietary RS on selected brain and behavioral functions in adult and aged rodents. Because glucokinase (GK) expression in hypothalamic arcuate nucleus and area postrema of the brainstem is important for brain glucose sensing, GK mRNA was measured by brain nuclei microdissection and PCR. Adult RS-fed rats had a higher GK mRNA than controls in both brain nuclei, an indicator of improved brain glucose sensing. Next, we tested whether dietary RS improve selected behaviors in aged mice. RS-fed aged mice exhibited (i) an increased eating responses to fasting, a behavioral indicator of improvement in aged brain glucose sensing; (ii) a longer latency to fall from an accelerating rotarod, a behavioral indicator of improved motor coordination; and (iii) a higher serum active glucagon-like peptide-1 (GLP-1). Then, GLP-1 receptor null (GLP-1RKO) mice were used to test the role of GLP-1 in brain glucose sensing, and they exhibited impaired eating responses to fasting. We conclude that in rodents (i) dietary RS improves two important indicators of brain function: glucose sensing and motor coordination, and (ii) GLP-1 is important in the optimal feeding response to a fast.

  17. Age-and Brain Region-Specific Differences in Mitochondrial ...

    EPA Pesticide Factsheets

    Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cerebellum (CER), striatum (STR), hippocampus (HIP)] of four diverse age groups [1 Month (young), 4 Month (adult), 12 Month (middle-aged), 24 Month (old age)] to understand age-related differences in selected brain regions and their contribution to age-related chemical sensitivity. Mitochondrial bioenergetics parameters and enzyme activity were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State 111 respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V1 and V2) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12 and 24 Month age groups. Activities of mitochondrial pyruvate dehydrogenase complex (PDHC) and electron transport chain (ETC) complexes I, II, and IV enzymes were also age- and brain-region specific. In general changes associated with age were more pronounced, with

  18. Extrinsic and Intrinsic Brain Network Connectivity Maintains Cognition across the Lifespan Despite Accelerated Decay of Regional Brain Activation

    PubMed Central

    Henson, Richard N.A.; Tyler, Lorraine K.; Razi, Adeel; Geerligs, Linda; Ham, Timothy E.; Rowe, James B.

    2016-01-01

    The maintenance of wellbeing across the lifespan depends on the preservation of cognitive function. We propose that successful cognitive aging is determined by interactions both within and between large-scale functional brain networks. Such connectivity can be estimated from task-free functional magnetic resonance imaging (fMRI), also known as resting-state fMRI (rs-fMRI). However, common correlational methods are confounded by age-related changes in the neurovascular signaling. To estimate network interactions at the neuronal rather than vascular level, we used generative models that specified both the neural interactions and a flexible neurovascular forward model. The networks' parameters were optimized to explain the spectral dynamics of rs-fMRI data in 602 healthy human adults from population-based cohorts who were approximately uniformly distributed between 18 and 88 years (www.cam-can.com). We assessed directed connectivity within and between three key large-scale networks: the salience network, dorsal attention network, and default mode network. We found that age influences connectivity both within and between these networks, over and above the effects on neurovascular coupling. Canonical correlation analysis revealed that the relationship between network connectivity and cognitive function was age-dependent: cognitive performance relied on neural dynamics more strongly in older adults. These effects were driven partly by reduced stability of neural activity within all networks, as expressed by an accelerated decay of neural information. Our findings suggest that the balance of excitatory connectivity between networks, and the stability of intrinsic neural representations within networks, changes with age. The cognitive function of older adults becomes increasingly dependent on these factors. SIGNIFICANCE STATEMENT Maintaining cognitive function is critical to successful aging. To study the neural basis of cognitive function across the lifespan, we studied a

  19. Ultraweak chemiluminescence of rice seeds during accelerated aging

    NASA Astrophysics Data System (ADS)

    Chen, Wenli; Xing, Da; He, Yonghong

    2002-04-01

    Ultraweak Chemiluminescence (UCL) studies of different aging degree of rice (Oryza sativa L.) seeds stored in a high temperature 40 degree(s)C and high relative humidity 90% environment (0 day, 8 days, 15 days, and 22 days) were carried out. We firstly observed that aging degree of rice seeds was positive correlation with ultraweak chemiluminescence during the early imbibition (0-1h). Addition of water to rice seeds stimulates ultraweak chemiluminescence, the intensity of which depends upon aging degree of seeds. The shorter the seed accelerated aging time was, the higher the intensity of the UCL in the early imbibition period, the lower hydrogen peroxide (H2O2) concentration of rice seeds, the higher percentage seed germination. The germination and superoxide dismutase (SOD) activity of dry rice seeds was obvious positive correlation with the intensity of UCL. While catalase (CAT) activity of rice seeds was determined. Mechanism of ultraweak chemiluminescence was discussed. It was concluded that the store time of rice seeds could be judged from their UCL characters during the early imbibition period, which might be a way to examine vigor of seeds.

  20. Want a Sharper Brain as You Age? Volunteer!

    MedlinePlus

    ... 162899.html Want a Sharper Brain as You Age? Volunteer! Study finds slight improvement in thinking and ... may have slightly sharper mental skills at the age of 50, a new study suggests. British researchers ...

  1. Trajectories of brain aging in middle-aged and older adults: regional and individual differences.

    PubMed

    Raz, Naftali; Ghisletta, Paolo; Rodrigue, Karen M; Kennedy, Kristen M; Lindenberger, Ulman

    2010-06-01

    The human brain changes with age. However, the rate and the trajectories of change vary among the brain regions and among individuals, and the reasons for these differences are unclear. In a sample of healthy middle-aged and older adults, we examined mean volume change and individual differences in the rate of change in 12 regional brain volumes over approximately 30 months. In addition to the baseline assessment, there were two follow-ups, 15 months apart. We observed significant average shrinkage of the hippocampus, entorhinal cortex, orbital-frontal cortex, and cerebellum in each of the intervals. Shrinkage of the hippocampus accelerated with time, whereas shrinkage of the caudate nucleus, prefrontal subcortical white matter, and corpus callosum emerged only at the second follow-up. Throughout both assessment intervals, the mean volumes of the lateral prefrontal and primary visual cortices, putamen, and pons did not change. Significant individual differences in shrinkage rates were observed in the lateral prefrontal cortex, the cerebellum, and all the white matter regions throughout the study, whereas additional regions (medial-temporal structures, the insula, and the basal ganglia) showed significant individual variation in change during the second follow-up. No individual variability was noted in the change of orbital frontal and visual cortices. In two white matter regions, we were able to identify factors associated with individual differences in brain shrinkage. In corpus callosum, shrinkage rate was greater in persons with hypertension, and in the pons, women and carriers of the ApoEepsilon4 allele exhibited declines not noted in the whole sample.

  2. Trajectories of brain aging in middle-aged and older adults: Regional and individual differences

    PubMed Central

    Raz, Naftali; Ghisletta, Paolo; Rodrigue, Karen M.; Kennedy, Kristen M.; Lindenberger, Ulman

    2010-01-01

    The human brain changes with age. However, the rate and the trajectories of change vary among the brain regions and among individuals, and the reasons for these differences are unclear. In a sample of healthy middle-aged and older adults, we examined mean volume change and individual differences in the rate of change in 12 regional brain volumes over approximately 30 months. In addition to the baseline assessment, there were two follow-ups, 15 months apart. We observed significant average shrinkage of the hippocampus, entorhinal cortex, orbital–frontal cortex, and cerebellum in each of the intervals. Shrinkage of the hippocampus accelerated with time, whereas shrinkage of the caudate nucleus, prefrontal subcortical white matter, and corpus callosum emerged only at the second follow-up. Throughout both assessment intervals, the mean volumes of the lateral prefrontal and primary visual cortices, putamen, and pons did not change. Significant individual differences in shrinkage rates were observed in the lateral prefrontal cortex, the cerebellum, and all the white matter regions throughout the study, whereas additional regions (medial–temporal structures, the insula, and the basal ganglia) showed significant individual variation in change during the second follow-up. No individual variability was noted in the change of orbital frontal and visual cortices. In two white matter regions, we were able to identify factors associated with individual differences in brain shrinkage. In corpus callosum, shrinkage rate was greater in persons with hypertension, and in the pons, women and carriers of the ApoEε4 allele exhibited declines not noted in the whole sample. PMID:20298790

  3. Tissue-specific accelerated aging in nucleotide excision repair deficiency

    PubMed Central

    Niedernhofer, Laura J.

    2008-01-01

    Nucleotide excision repair (NER) is a multi-step DNA repair mechanism that removes helix-distorting modified nucleotides from the genome. NER is divided into two subpathways depending on the location of DNA damage in the genome and how it is first detected. Global genome NER identifies and repairs DNA lesions throughout the genome. This subpathway of NER primarily protects against the accumulation of mutations in the genome. Transcription-coupled (TC) NER rapidly repairs lesions in the transcribed strand of DNA that block transcription by RNA polymerase II. TC-NER prevents cell death in response to stalled transcription. Defects in NER cause three distinct human diseases: xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Each of these syndromes is characterized by premature onset of pathologies that overlap with those associated with old age in humans. This reveals the contribution of DNA damage to multiple age-related diseases. Tissues affected include the skin, eye, bone marrow, nervous system and endocrine axis. This review emphasizes accelerated aging associated with xeroderma pigmentosum and discusses the cause of these pathologies, either mutation accumulation or cell death as a consequence of failure to repair DNA damage. PMID:18538374

  4. Accelerated Aging System for Prognostics of Power Semiconductor Devices

    NASA Technical Reports Server (NTRS)

    Celaya, Jose R.; Vashchenko, Vladislav; Wysocki, Philip; Saha, Sankalita

    2010-01-01

    Prognostics is an engineering discipline that focuses on estimation of the health state of a component and the prediction of its remaining useful life (RUL) before failure. Health state estimation is based on actual conditions and it is fundamental for the prediction of RUL under anticipated future usage. Failure of electronic devices is of great concern as future aircraft will see an increase of electronics to drive and control safety-critical equipment throughout the aircraft. Therefore, development of prognostics solutions for electronics is of key importance. This paper presents an accelerated aging system for gate-controlled power transistors. This system allows for the understanding of the effects of failure mechanisms, and the identification of leading indicators of failure which are essential in the development of physics-based degradation models and RUL prediction. In particular, this system isolates electrical overstress from thermal overstress. Also, this system allows for a precise control of internal temperatures, enabling the exploration of intrinsic failure mechanisms not related to the device packaging. By controlling the temperature within safe operation levels of the device, accelerated aging is induced by electrical overstress only, avoiding the generation of thermal cycles. The temperature is controlled by active thermal-electric units. Several electrical and thermal signals are measured in-situ and recorded for further analysis in the identification of leading indicators of failures. This system, therefore, provides a unique capability in the exploration of different failure mechanisms and the identification of precursors of failure that can be used to provide a health management solution for electronic devices.

  5. Is the brain's inertia for motor movement different for acceleration and deceleration?

    NASA Astrophysics Data System (ADS)

    Adhikari, Bhim; Quinn, Kristen; Dhamala, Mukeshwar

    2009-11-01

    The brain's ability to synchronize movement with external cues is used daily, yet neuroscience is far from a full understanding of the processes that allow these simple sequential performances. This experimental design was implemented to determine differences in brain activity when finger tapping at increasing and decreasing rhythms. Eight subjects tapped their right index finger on a response box following visual cues projected on a screen during an fMRI session. Isolating continuous and discrete finger tapping (sinusoidal variation of rate and step-like variation) decelerations versus accelerations revealed much greater activity in the left and right primary motor cortices when completing the sinusoidal rhythm task. Decelerating rates recruited distributed regions of the brain in contrast to brain stimulation during accelerating rates. These results suggest that the brain's inertia for movement is different for acceleration and deceleration.

  6. The influence of acceleration loading curve characteristics on traumatic brain injury.

    PubMed

    Post, Andrew; Blaine Hoshizaki, T; Gilchrist, Michael D; Brien, Susan; Cusimano, Michael D; Marshall, Shawn

    2014-03-21

    To prevent brain trauma, understanding the mechanism of injury is essential. Once the mechanism of brain injury has been identified, prevention technologies could then be developed to aid in their prevention. The incidence of brain injury is linked to how the kinematics of a brain injury event affects the internal structures of the brain. As a result it is essential that an attempt be made to describe how the characteristics of the linear and rotational acceleration influence specific traumatic brain injury lesions. As a result, the purpose of this study was to examine the influence of the characteristics of linear and rotational acceleration pulses and how they account for the variance in predicting the outcome of TBI lesions, namely contusion, subdural hematoma (SDH), subarachnoid hemorrhage (SAH), and epidural hematoma (EDH) using a principal components analysis (PCA). Monorail impacts were conducted which simulated falls which caused the TBI lesions. From these reconstructions, the characteristics of the linear and rotational acceleration were determined and used for a PCA analysis. The results indicated that peak resultant acceleration variables did not account for any of the variance in predicting TBI lesions. The majority of the variance was accounted for by duration of the resultant and component linear and rotational acceleration. In addition, the components of linear and rotational acceleration characteristics on the x, y, and z axes accounted for the majority of the remainder of the variance after duration.

  7. Untangling the Effect of Head Acceleration on Brain Responses to Blast Waves.

    PubMed

    Mao, Haojie; Unnikrishnan, Ginu; Rakesh, Vineet; Reifman, Jaques

    2015-12-01

    Multiple injury-causing mechanisms, such as wave propagation, skull flexure, cavitation, and head acceleration, have been proposed to explain blast-induced traumatic brain injury (bTBI). An accurate, quantitative description of the individual contribution of each of these mechanisms may be necessary to develop preventive strategies against bTBI. However, to date, despite numerous experimental and computational studies of bTBI, this question remains elusive. In this study, using a two-dimensional (2D) rat head model, we quantified the contribution of head acceleration to the biomechanical response of brain tissues when exposed to blast waves in a shock tube. We compared brain pressure at the coup, middle, and contre-coup regions between a 2D rat head model capable of simulating all mechanisms (i.e., the all-effects model) and an acceleration-only model. From our simulations, we determined that head acceleration contributed 36-45% of the maximum brain pressure at the coup region, had a negligible effect on the pressure at the middle region, and was responsible for the low pressure at the contre-coup region. Our findings also demonstrate that the current practice of measuring rat brain pressures close to the center of the brain would record only two-thirds of the maximum pressure observed at the coup region. Therefore, to accurately capture the effects of acceleration in experiments, we recommend placing a pressure sensor near the coup region, especially when investigating the acceleration mechanism using different experimental setups.

  8. Telomere Recombination Accelerates Cellular Aging in Saccharomyces cerevisiae

    PubMed Central

    Chen, Xiao-Fen; Meng, Fei-Long; Zhou, Jin-Qiu

    2009-01-01

    Telomeres are nucleoprotein structures located at the linear ends of eukaryotic chromosomes. Telomere integrity is required for cell proliferation and survival. Although the vast majority of eukaryotic species use telomerase as a primary means for telomere maintenance, a few species can use recombination or retrotransposon-mediated maintenance pathways. Since Saccharomyces cerevisiae can use both telomerase and recombination to replicate telomeres, budding yeast provides a useful system with which to examine the evolutionary advantages of telomerase and recombination in preserving an organism or cell under natural selection. In this study, we examined the life span in telomerase-null, post-senescent type II survivors that have employed homologous recombination to replicate their telomeres. Type II recombination survivors stably maintained chromosomal integrity but exhibited a significantly reduced replicative life span. Normal patterns of cell morphology at the end of a replicative life span and aging-dependent sterility were observed in telomerase-null type II survivors, suggesting the type II survivors aged prematurely in a manner that is phenotypically consistent with that of wild-type senescent cells. The shortened life span of type II survivors was extended by calorie restriction or TOR1 deletion, but not by Fob1p inactivation or Sir2p over-expression. Intriguingly, rDNA recombination was decreased in type II survivors, indicating that the premature aging of type II survivors was not caused by an increase in extra-chromosomal rDNA circle accumulation. Reintroduction of telomerase activity immediately restored the replicative life span of type II survivors despite their heterogeneous telomeres. These results suggest that telomere recombination accelerates cellular aging in telomerase-null type II survivors and that telomerase is likely a superior telomere maintenance pathway in sustaining yeast replicative life span. PMID:19557187

  9. The aging brain: the cognitive reserve hypothesis and hominid evolution.

    PubMed

    Allen, John S; Bruss, Joel; Damasio, Hanna

    2005-01-01

    Compared to other primates, humans live a long time and have large brains. Recent theories of the evolution of human life history stages (grandmother hypothesis, intergenerational transfer of information) lend credence to the notion that selection for increased life span and menopause has occurred in hominid evolution, despite the reduction in the force of natural selection operating on older, especially post-reproductive, individuals. Theories that posit the importance (in an inclusive fitness sense) of the survival of older individuals require them to maintain a reasonably high level of cognitive function (e.g., memory, communication). Patterns of brain aging and factors associated with healthy brain aging should be relevant to this issue. Recent neuroimaging research suggests that, in healthy aging, human brain volume (gray and white matter) is well-maintained until at least 60 years of age; cognitive function also shows only nonsignificant declines at this age. The maintenance of brain volume and cognitive performance is consistent with the idea of a significant post- or late-reproductive life history stage. A clinical model, "the cognitive reserve hypothesis," proposes that both increased brain volume and enhanced cognitive ability may contribute to healthy brain aging, reducing the likelihood of developing dementia. Selection for increased brain size and increased cognitive ability in hominid evolution may therefore have been important in selection for increased lifespan in the context of intergenerational social support networks.

  10. Plasticity of the aging brain: new directions in cognitive neuroscience.

    PubMed

    Gutchess, Angela

    2014-10-31

    Cognitive neuroscience has revealed aging of the human brain to be rich in reorganization and change. Neuroimaging results have recast our framework around cognitive aging from one of decline to one emphasizing plasticity. Current methods use neurostimulation approaches to manipulate brain function, providing a direct test of the ways that the brain differently contributes to task performance for younger and older adults. Emerging research into emotional, social, and motivational domains provides some evidence for preservation with age, suggesting potential avenues of plasticity, alongside additional evidence for reorganization. Thus, we begin to see that aging of the brain, amidst interrelated behavioral and biological changes, is as complex and idiosyncratic as the brain itself, qualitatively changing over the life span.

  11. Accelerated aging in the tumor microenvironment: connecting aging, inflammation and cancer metabolism with personalized medicine.

    PubMed

    Lisanti, Michael P; Martinez-Outschoorn, Ubaldo E; Pavlides, Stephanos; Whitaker-Menezes, Diana; Pestell, Richard G; Howell, Anthony; Sotgia, Federica

    2011-07-01

    Cancer is thought to be a disease associated with aging. Interestingly, normal aging is driven by the production of ROS and mitochondrial oxidative stress, resulting in the cumulative accumulation of DNA damage. Here, we discuss how ROS signaling, NFκB- and HIF1-activation in the tumor microenvironment induces a form of "accelerated aging," which leads to stromal inflammation and changes in cancer cell metabolism. Thus, we present a unified model where aging (ROS), inflammation (NFκB) and cancer metabolism (HIF1), act as co-conspirators to drive autophagy ("self-eating") in the tumor stroma. Then, autophagy in the tumor stroma provides high-energy "fuel" and the necessary chemical building blocks, for accelerated tumor growth and metastasis. Stromal ROS production acts as a "mutagenic motor" and allows cancer cells to buffer-at a distance-exactly how much of a mutagenic stimulus they receive, further driving tumor cell selection and evolution. Surviving cancer cells would be selected for the ability to induce ROS more effectively in stromal fibroblasts, so they could extract more nutrients from the stroma via autophagy. If lethal cancer is a disease of "accelerated host aging" in the tumor stroma, then cancer patients may benefit from therapy with powerful antioxidants. Antioxidant therapy should block the resulting DNA damage, and halt autophagy in the tumor stroma, effectively "cutting off the fuel supply" for cancer cells. These findings have important new implications for personalized cancer medicine, as they link aging, inflammation and cancer metabolism with novel strategies for more effective cancer diagnostics and therapeutics.

  12. Do glutathione levels decline in aging human brain?

    PubMed

    Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

    2016-04-01

    For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain.

  13. [The use of biological age on mental work capacity model in accelerated aging assessment of professional lorry-drivers].

    PubMed

    Bashkireva, A S

    2012-01-01

    The studies of biological age, aging rate, mental work capacity in professional drivers were conducted. The examination revealed peculiarities of system organization of functions determining the mental work capacity levels. Dynamics of the aging process of professional driver's organism in relation with calendar age and driving experience were shown using the biological age model. The results point at the premature decrease of the mental work capacity in professional drivers. It was proved, that premature age-related changes of physiologic and psychophysiologic indices in drivers are just "risk indicators", while long driving experience is a real risk factor, accelerating the aging process. The "risk group" with manifestations of accelerating aging was observed in 40-49-year old drivers with 15-19 years of professional experience. The expediency of using the following methods for the age rate estimation according to biologic age indices and necessity of prophylactic measures for premature and accelerated aging prevention among working population was demonstrated.

  14. Neurodevelopmental Versus Neurodegenerative Model of Schizophrenia and Bipolar Disorder: Comparison with Physiological Brain Development and Aging.

    PubMed

    Buoli, Massimiliano; Serati, Marta; Caldiroli, Alice; Cremaschi, Laura; Altamura, Alfredo Carlo

    2017-03-01

    Available data support a contribution of both neurodevelopmental and neurodegenerative factors in the etiology of schizophrenia (SCH) and bipolar disorder (BD). Of note, one of the most important issue of the current psychiatric research is to identify the specific factors that contribute to impaired brain development and neurodegeneration in SCH and BD, and especially how these factors alter normal brain development and physiological aging process. Our hypothesis is that only specific damages, taking place in precise brain development stages, are associated with future SCH /BD onset and that neurodegeneration consists of an acceleration of brain aging after SCH /BD onset. In support of our hypothesis, the results of the present narrative mini-review shows as neurodevelopmental damages generally contribute to neuropsychiatric syndromes (e.g. hypothyroidism or treponema pallidum), but only some of them are specifically associated with adult SCH and BD (e.g. toxoplasma or substance abuse), particularly if they happen in specific stages of brain development. On the other hand, cognitive impairment and brain changes, associated with long duration of SCH /BD, look like what happens during aging: memory, executive domains and prefrontal cortex are implicated both in aging and in SCH /BD progression. Future research will explore possible validity of this etiological model for SCH and BD.

  15. Diabetes exacerbates amyloid and neurovascular pathology in aging-accelerated mice.

    PubMed

    Currais, Antonio; Prior, Marguerite; Lo, David; Jolivalt, Corinne; Schubert, David; Maher, Pamela

    2012-12-01

    Mounting evidence supports a link between diabetes, cognitive dysfunction, and aging. However, the physiological mechanisms by which diabetes impacts brain function and cognition are not fully understood. To determine how diabetes contributes to cognitive dysfunction and age-associated pathology, we used streptozotocin to induce type 1 diabetes (T1D) in senescence-accelerated prone 8 (SAMP8) and senescence-resistant 1 (SAMR1) mice. Contextual fear conditioning demonstrated that T1D resulted in the development of cognitive deficits in SAMR1 mice similar to those seen in age-matched, nondiabetic SAMP8 mice. No further cognitive deficits were observed when the SAMP8 mice were made diabetic. T1D dramatically increased Aβ and glial fibrillary acidic protein immunoreactivity in the hippocampus of SAMP8 mice and to a lesser extent in age-matched SAMR1 mice. Further analysis revealed aggregated Aβ within astrocyte processes surrounding vessels. Western blot analyses from T1D SAMP8 mice showed elevated amyloid precursor protein processing and protein glycation along with increased inflammation. T1D elevated tau phosphorylation in the SAMR1 mice but did not further increase it in the SAMP8 mice where it was already significantly higher. These data suggest that aberrant glucose metabolism potentiates the aging phenotype in old mice and contributes to early stage central nervous system pathology in younger animals.

  16. A Phase I Study of Short-Course Accelerated Whole Brain Radiation Therapy for Multiple Brain Metastases

    SciTech Connect

    Caravatta, Luciana; Deodato, Francesco; Ferro, Marica; Macchia, Gabriella; Massaccesi, Mariangela; Cilla, Savino; Padula, Gilbert D.A.; Mignogna, Samantha; Tambaro, Rosa; Carrozza, Francesco; Flocco, Mariano; Cantore, Giampaolo; Scapati, Andrea; Buwenge, Milly; and others

    2012-11-15

    Purpose: To define the maximum tolerated dose (MTD) of a SHort-course Accelerated whole brain RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. Methods and Materials: A phase 1 trial in 4 dose-escalation steps was designed: 12 Gy (3 Gy per fraction), 14 Gy (3.5 Gy per fraction), 16 Gy (4 Gy per fraction), and 18 Gy (4.5 Gy per fraction). Eligibility criteria included patients with unfavorable recursive partitioning analysis (RPA) class > or =2 with at least 3 brain metastases or metastatic disease in more than 3 organ systems, and Eastern Cooperative Oncology Group (ECOG) performance status {<=}3. Treatment was delivered in 2 days with twice-daily fractionation. Patients were treated in cohorts of 6-12 to define the MTD. The dose-limiting toxicity (DLT) was defined as any acute toxicity {>=}grade 3, according to the Radiation Therapy Oncology Group scale. Information on the status of the main neurologic symptoms and quality of life were recorded. Results: Characteristics of the 49 enrolled patients were as follows: male/female, 30/19; median age, 66 years (range, 23-83 years). ECOG performance status was <3 in 46 patients (94%). Fourteen patients (29%) were considered to be in recursive partitioning analysis (RPA) class 3. Grade 1-2 acute neurologic (26.4%) and skin (18.3%) toxicities were recorded. Only 1 patient experienced DLT (neurologic grade 3 acute toxicity). With a median follow-up time of 5 months (range, 1-23 months), no late toxicities have been observed. Three weeks after treatment, 16 of 21 symptomatic patients showed an improvement or resolution of presenting symptoms (overall symptom response rate, 76.2%; confidence interval 0.95: 60.3-95.9%). Conclusions: Short-course accelerated radiation therapy in twice-daily fractions for 2 consecutive days is tolerated up to a total dose of 18 Gy. A phase 2 study has been planned to evaluate the efficacy on overall survival, symptom control, and quality of life indices.

  17. Spectral Variability in the Aged Brain during Fine Motor Control

    PubMed Central

    Quandt, Fanny; Bönstrup, Marlene; Schulz, Robert; Timmermann, Jan E.; Zimerman, Maximo; Nolte, Guido; Hummel, Friedhelm C.

    2016-01-01

    Physiological aging is paralleled by a decline of fine motor skills accompanied by structural and functional alterations of the underlying brain network. Here, we aim to investigate age-related changes in the spectral distribution of neuronal oscillations during fine skilled motor function. We employ the concept of spectral entropy in order to describe the flatness and peaked-ness of a frequency spectrum to quantify changes in the spectral distribution of the oscillatory motor response in the aged brain. Electroencephalogram was recorded in elderly (n = 32) and young (n = 34) participants who performed either a cued finger movement or a pinch or a whole hand grip task with their dominant right hand. Whereas young participant showed distinct, well-defined movement-related power decreases in the alpha and upper beta band, elderly participants exhibited a flat broadband, frequency-unspecific power desynchronization. This broadband response was reflected by an increase of spectral entropy over sensorimotor and frontal areas in the aged brain. Neuronal activation patterns differed between motor tasks in the young brain, while the aged brain showed a similar activation pattern in all tasks. Moreover, we found a wider recruitment of the cortical motor network in the aged brain. The present study adds to the understanding of age-related changes of neural coding during skilled motor behavior, revealing a less predictable signal with great variability across frequencies in a wide cortical motor network in the aged brain. The increase in entropy in the aged brain could be a reflection of random noise-like activity or could represent a compensatory mechanism that serves a functional role. PMID:28066231

  18. Spectral Variability in the Aged Brain during Fine Motor Control.

    PubMed

    Quandt, Fanny; Bönstrup, Marlene; Schulz, Robert; Timmermann, Jan E; Zimerman, Maximo; Nolte, Guido; Hummel, Friedhelm C

    2016-01-01

    Physiological aging is paralleled by a decline of fine motor skills accompanied by structural and functional alterations of the underlying brain network. Here, we aim to investigate age-related changes in the spectral distribution of neuronal oscillations during fine skilled motor function. We employ the concept of spectral entropy in order to describe the flatness and peaked-ness of a frequency spectrum to quantify changes in the spectral distribution of the oscillatory motor response in the aged brain. Electroencephalogram was recorded in elderly (n = 32) and young (n = 34) participants who performed either a cued finger movement or a pinch or a whole hand grip task with their dominant right hand. Whereas young participant showed distinct, well-defined movement-related power decreases in the alpha and upper beta band, elderly participants exhibited a flat broadband, frequency-unspecific power desynchronization. This broadband response was reflected by an increase of spectral entropy over sensorimotor and frontal areas in the aged brain. Neuronal activation patterns differed between motor tasks in the young brain, while the aged brain showed a similar activation pattern in all tasks. Moreover, we found a wider recruitment of the cortical motor network in the aged brain. The present study adds to the understanding of age-related changes of neural coding during skilled motor behavior, revealing a less predictable signal with great variability across frequencies in a wide cortical motor network in the aged brain. The increase in entropy in the aged brain could be a reflection of random noise-like activity or could represent a compensatory mechanism that serves a functional role.

  19. Exploring age-related brain degeneration in meditation practitioners.

    PubMed

    Luders, Eileen

    2014-01-01

    A growing body of research suggests that meditation practices are associated with substantial psychological as well as physiological benefits. In searching for the biological mechanisms underlying the beneficial impact of meditation, studies have revealed practice-induced alterations of neurotransmitters, brain activity, and cognitive abilities, just to name a few. These findings not only imply a close link between meditation and brain structure, but also suggest possible modulating effects of meditation on age-related brain atrophy. Given that normal aging is associated with significant loss of brain tissue, meditation-induced growth and/or preservation might manifest as a seemingly reduced brain age in meditators (i.e., cerebral measures characteristic of younger brains). Surprisingly, there are only three published studies that have addressed the question of whether meditation diminishes age-related brain degeneration. This paper reviews these three studies with respect to the brain attributes studied, the analytical strategies applied, and the findings revealed. The review concludes with an elaborate discussion on the significance of existing studies, implications and directions for future studies, as well as the overall relevance of this field of research.

  20. Modeling the brain morphology distribution in the general aging population

    NASA Astrophysics Data System (ADS)

    Huizinga, W.; Poot, D. H. J.; Roshchupkin, G.; Bron, E. E.; Ikram, M. A.; Vernooij, M. W.; Rueckert, D.; Niessen, W. J.; Klein, S.

    2016-03-01

    Both normal aging and neurodegenerative diseases such as Alzheimer's disease cause morphological changes of the brain. To better distinguish between normal and abnormal cases, it is necessary to model changes in brain morphology owing to normal aging. To this end, we developed a method for analyzing and visualizing these changes for the entire brain morphology distribution in the general aging population. The method is applied to 1000 subjects from a large population imaging study in the elderly, from which 900 were used to train the model and 100 were used for testing. The results of the 100 test subjects show that the model generalizes to subjects outside the model population. Smooth percentile curves showing the brain morphology changes as a function of age and spatiotemporal atlases derived from the model population are publicly available via an interactive web application at agingbrain.bigr.nl.

  1. Lipidomics of human brain aging and Alzheimer's disease pathology.

    PubMed

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context.

  2. Brain Damage in School Age Children.

    ERIC Educational Resources Information Center

    Haywood, H. Carl, Ed.

    The product of a professional workshop, 10 papers discuss brain damage. An introduction to clinical neuropsychology is presented by H. Carl Haywood. A section on neurological foundations includes papers on the organization of the central nervous system by Jack T. Tapp and Lance L. Simpson, on epilepsy by Angela T. Folsom, and on organic language…

  3. Statistical Approaches for the Study of Cognitive and Brain Aging

    PubMed Central

    Chen, Huaihou; Zhao, Bingxin; Cao, Guanqun; Proges, Eric C.; O'Shea, Andrew; Woods, Adam J.; Cohen, Ronald A.

    2016-01-01

    Neuroimaging studies of cognitive and brain aging often yield massive datasets that create many analytic and statistical challenges. In this paper, we discuss and address several limitations in the existing work. (1) Linear models are often used to model the age effects on neuroimaging markers, which may be inadequate in capturing the potential nonlinear age effects. (2) Marginal correlations are often used in brain network analysis, which are not efficient in characterizing a complex brain network. (3) Due to the challenge of high-dimensionality, only a small subset of the regional neuroimaging markers is considered in a prediction model, which could miss important regional markers. To overcome those obstacles, we introduce several advanced statistical methods for analyzing data from cognitive and brain aging studies. Specifically, we introduce semiparametric models for modeling age effects, graphical models for brain network analysis, and penalized regression methods for selecting the most important markers in predicting cognitive outcomes. We illustrate these methods using the healthy aging data from the Active Brain Study. PMID:27486400

  4. Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging.

    PubMed

    Zamroziewicz, Marta K; Barbey, Aron K

    2016-01-01

    Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition's impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition-from entire diets to specific nutrients-affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i) methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns (NBPs), along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI). By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging.

  5. Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging

    PubMed Central

    Zamroziewicz, Marta K.; Barbey, Aron K.

    2016-01-01

    Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition's impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition—from entire diets to specific nutrients—affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i) methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns (NBPs), along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI). By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging. PMID:27375409

  6. Transcriptomic insights into human brain evolution: acceleration, neutrality, heterochrony.

    PubMed

    Somel, Mehmet; Rohlfs, Rori; Liu, Xiling

    2014-12-01

    Primate brain transcriptome comparisons within the last 12 years have yielded interesting but contradictory observations on how the transcriptome evolves, and its adaptive role in human cognitive evolution. Since the human-chimpanzee common ancestor, the human prefrontal cortex transcriptome seems to have evolved more than that of the chimpanzee. But at the same time, most expression differences among species, especially those observed in adults, appear as consequences of neutral evolution at cis-regulatory sites. Adaptive expression changes in the human brain may be rare events involving timing shifts, or heterochrony, in specific neurodevelopmental processes. Disentangling adaptive and neutral expression changes, and associating these with human-specific features of the brain require improved methods, comparisons across more species, and further work on comparative development.

  7. Emotion and aging: evidence from brain and behavior

    PubMed Central

    Ebner, Natalie C.; Fischer, Håkan

    2014-01-01

    Emotions play a central role in every human life from the moment we are born until we die. They prepare the body for action, highlight what should be noticed and remembered, and guide decisions and actions. As emotions are central to daily functioning, it is important to understand how aging affects perception, memory, experience, as well as regulation of emotions. The Frontiers research topic Emotion and Aging: Evidence from Brain and Behavior takes a step into uncovering emotional aging considering both brain and behavioral processes. The contributions featured in this issue adopt innovative theoretical perspectives and use novel methodological approaches to target a variety of topics that can be categorized into three overarching questions: How do cognition and emotion interact in aging in brain and behavior? What are behavioral and brain-related moderators of emotional aging? Does emotion-regulatory success as reflected in brain and behavior change with age? In this perspective paper we discuss theoretical innovation, methodological approach, and scientific advancement of the 13 papers in the context of the broader literature on emotional aging. We conclude by reflecting on topics untouched and future directions to take. PMID:25250002

  8. BRAIN FUEL METABOLISM, AGING AND ALZHEIMER’S DISEASE

    PubMed Central

    Cunnane, SC; Nugent, S; Roy, M; Courchesne-Loyer, A; Croteau, E; Tremblay, S; Castellano, A; Pifferi, F; Bocti, C; Paquet, N; Begdouri, H; Bentourkia, M; Turcotte, E; Allard, M; Barberger-Gateau, P; Fulop, T; Rapoport, S

    2012-01-01

    Lower brain glucose metabolism is present before the onset of clinically-measurable cognitive decline in two groups of people at risk of Alzheimer’s disease (AD) - carriers of apoE4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and contribute to the neuropathological cascade leading cognitive decline in AD. The reason for brain hypometabolism is unclear but may include defects in glucose transport at the blood-brain barrier, glycolysis, and/or mitochondrial function. Methodological issues presently preclude knowing with certainty whether or not aging in the absence of cognitive impairment is necessarily associated with lower brain glucose metabolism. Nevertheless, aging appears to increase the risk of deteriorating systemic control of glucose utilization which, in turn, may increase the risk of declining brain glucose uptake, at least in some regions. A contributing role of deteriorating glucose availability to or metabolism by the brain in AD does not exclude the opposite effect, i.e. that neurodegenerative processes in AD further decrease brain glucose metabolism because of reduced synaptic functionality and, hence, reduced energy needs, thereby completing a vicious cycle. Strategies to reduce the risk of AD by breaking this cycle should aim to – (i) improve insulin sensitivity by improving systemic glucose utilization, or (ii) bypass deteriorating brain glucose metabolism using approaches that safely induce mild, sustainable ketonemia. PMID:21035308

  9. Influence of age on brain edema formation, secondary brain damage and inflammatory response after brain trauma in mice.

    PubMed

    Timaru-Kast, Ralph; Luh, Clara; Gotthardt, Philipp; Huang, Changsheng; Schäfer, Michael K; Engelhard, Kristin; Thal, Serge C

    2012-01-01

    After traumatic brain injury (TBI) elderly patients suffer from higher mortality rate and worse functional outcome compared to young patients. However, experimental TBI research is primarily performed in young animals. Aim of the present study was to clarify whether age affects functional outcome, neuroinflammation and secondary brain damage after brain trauma in mice. Young (2 months) and old (21 months) male C57Bl6N mice were anesthetized and subjected to a controlled cortical impact injury (CCI) on the right parietal cortex. Animals of both ages were randomly assigned to 15 min, 24 h, and 72 h survival. At the end of the observation periods, contusion volume, brain water content, neurologic function, cerebral and systemic inflammation (CD3+ T cell migration, inflammatory cytokine expression in brain and lung, blood differential cell count) were determined. Old animals showed worse neurological function 72 h after CCI and a high mortality rate (19.2%) compared to young (0%). This did not correlate with histopathological damage, as contusion volumes were equal in both age groups. Although a more pronounced brain edema formation was detected in old mice 24 hours after TBI, lack of correlation between brain water content and neurological deficit indicated that brain edema formation is not solely responsible for age-dependent differences in neurological outcome. Brains of old naïve mice were about 8% smaller compared to young naïve brains, suggesting age-related brain atrophy with possible decline in plasticity. Onset of cerebral inflammation started earlier and primarily ipsilateral to damage in old mice, whereas in young mice inflammation was delayed and present in both hemispheres with a characteristic T cell migration pattern. Pulmonary interleukin 1β expression was up-regulated after cerebral injury only in young, not aged mice. The results therefore indicate that old animals are prone to functional deficits and strong ipsilateral cerebral inflammation

  10. Metabolism of choline in brain of the aged CBF-1 mouse

    SciTech Connect

    Saito, M.; Kindel, G.; Karczmar, A.G.; Rosenberg, A.

    1986-01-01

    In order to quantify the changes that occur in the cholinergic central nervous system with aging, we have compared acetylcholine (Ach) formation in brain cortex slice preparations from 2-year-old aged CBF-1 mouse brains and compared the findings with those in 2-4-month-old young adult mouse brain slices. Incorporation of exogenous radioactively labelled choline (31 nM (/sup 3/H) choline) into acetyl choline in incubated brain slices was linear with time for 90 min. Percentage of total choline label distributed into Ach remained constant from 5 min after starting the incubation to 90 min. In contrast, distribution of label into intracellular free choline (Ch) and phosphorylcholine (Pch) changed continuously over this period suggesting that the Ch pool for Ach synthesis in brain cortex is different from that for Pch synthesis. Incorporation of radioactivity into Ach was not influenced by administration of 10 microM eserine, showing that the increment of radioactivity in Ach reflects rate of Ach formation, independently from degradation by acetylcholine esterases. Under our experimental conditions, slices from cortices of aged 24-month-old mouse brain showed a significantly greater (27%) incorporation of radioactivity into intracellular Ach than those from young, 2-4-month-old, brain cortices. Inhibitors of Ach release, 1 mM ATP or GABA, had no effect. Since concentration of radioactive precursor in the incubation medium was very low (31 nM), the Ch pool for Ach synthesis in slices was labelled without measurably changing the size of the endogenous pool. These data suggest a compensatory acceleration of Ach synthesis or else a smaller precursor pool specific for Ach synthesis into which labelled Ch migrated in aged brain.

  11. Is the brain's inertia for motor movements different for acceleration and deceleration?

    PubMed

    Adhikari, Bhim M; Quinn, Kristen M; Dhamala, Mukesh

    2013-01-01

    The brain's ability to synchronize movements with external cues is used daily, yet neuroscience is far from a full understanding of the brain mechanisms that facilitate and set behavioral limits on these sequential performances. This functional magnetic resonance imaging (fMRI) study was designed to help understand the neural basis of behavioral performance differences on a synchronizing movement task during increasing (acceleration) and decreasing (deceleration) metronome rates. In the MRI scanner, subjects were instructed to tap their right index finger on a response box in synchrony to visual cues presented on a display screen. The tapping rate varied either continuously or in discrete steps ranging from 0.5 Hz to 3 Hz. Subjects were able to synchronize better during continuously accelerating rhythms than in continuously or discretely decelerating rhythms. The fMRI data revealed that the precuneus was activated more during continuous deceleration than during acceleration with the hysteresis effect significant at rhythm rates above 1 Hz. From the behavioral data, two performance measures, tapping rate and synchrony index, were derived to further analyze the relative brain activity during acceleration and deceleration of rhythms. Tapping rate was associated with a greater brain activity during deceleration in the cerebellum, superior temporal gyrus and parahippocampal gyrus. Synchrony index was associated with a greater activity during the continuous acceleration phase than during the continuous deceleration or discrete acceleration phases in a distributed network of regions including the prefrontal cortex and precuneus. These results indicate that the brain's inertia for movement is different for acceleration and deceleration, which may have implications in understanding the origin of our perceptual and behavioral limits.

  12. Untangling the Effect of Head Acceleration on Brain Responses to Blast Waves

    PubMed Central

    Mao, Haojie; Unnikrishnan, Ginu; Rakesh, Vineet; Reifman, Jaques

    2015-01-01

    Multiple injury-causing mechanisms, such as wave propagation, skull flexure, cavitation, and head acceleration, have been proposed to explain blast-induced traumatic brain injury (bTBI). An accurate, quantitative description of the individual contribution of each of these mechanisms may be necessary to develop preventive strategies against bTBI. However, to date, despite numerous experimental and computational studies of bTBI, this question remains elusive. In this study, using a two-dimensional (2D) rat head model, we quantified the contribution of head acceleration to the biomechanical response of brain tissues when exposed to blast waves in a shock tube. We compared brain pressure at the coup, middle, and contre-coup regions between a 2D rat head model capable of simulating all mechanisms (i.e., the all-effects model) and an acceleration-only model. From our simulations, we determined that head acceleration contributed 36–45% of the maximum brain pressure at the coup region, had a negligible effect on the pressure at the middle region, and was responsible for the low pressure at the contre-coup region. Our findings also demonstrate that the current practice of measuring rat brain pressures close to the center of the brain would record only two-thirds of the maximum pressure observed at the coup region. Therefore, to accurately capture the effects of acceleration in experiments, we recommend placing a pressure sensor near the coup region, especially when investigating the acceleration mechanism using different experimental setups. PMID:26458125

  13. Berry fruit supplementation and the aging brain.

    PubMed

    Shukitt-Hale, Barbara; Lau, Francis C; Joseph, James A

    2008-02-13

    The onset of age-related neurodegenerative diseases such as Alzheimer's or Parkinson's disease, superimposed on a declining nervous system, could exacerbate the motor and cognitive behavioral deficits that normally occur in senescence. In cases of severe deficits in memory or motor function, hospitalization and/or custodial care would be a likely outcome. This means that unless some way is found to reduce these age-related decrements in neuronal function, health-care costs will continue to rise exponentially. Thus, it is extremely important to explore methods to retard or reverse age-related neuronal deficits, as well as their subsequent behavioral manifestations, to increase healthy aging. In this regard, consumption of diets rich in antioxidants and anti-inflammatory polyphenolics, such as those found in fruits and vegetables, may lower the risk of developing age-related neurodegenerative diseases. Research suggests that the polyphenolic compounds found in berry fruits, such as blueberries and strawberries, may exert their beneficial effects either through their ability to lower oxidative stress and inflammation or directly by altering the signaling involved in neuronal communication, calcium buffering ability, neuroprotective stress shock proteins, plasticity, and stress signaling pathways. These interventions, in turn, may exert protection against age-related deficits in cognitive and motor function. The purpose of this paper is to discuss the benefits of these interventions in rodent models and to describe the putative molecular mechanisms involved in their benefits.

  14. Normal brain ageing: models and mechanisms

    PubMed Central

    Toescu, Emil C

    2005-01-01

    Normal ageing is associated with a degree of decline in a number of cognitive functions. Apart from the issues raised by the current attempts to expand the lifespan, understanding the mechanisms and the detailed metabolic interactions involved in the process of normal neuronal ageing continues to be a challenge. One model, supported by a significant amount of experimental evidence, views the cellular ageing as a metabolic state characterized by an altered function of the metabolic triad: mitochondria–reactive oxygen species (ROS)–intracellular Ca2+. The perturbation in the relationship between the members of this metabolic triad generate a state of decreased homeostatic reserve, in which the aged neurons could maintain adequate function during normal activity, as demonstrated by the fact that normal ageing is not associated with widespread neuronal loss, but become increasingly vulnerable to the effects of excessive metabolic loads, usually associated with trauma, ischaemia or neurodegenerative processes. This review will concentrate on some of the evidence showing altered mitochondrial function with ageing and also discuss some of the functional consequences that would result from such events, such as alterations in mitochondrial Ca2+ homeostasis, ATP production and generation of ROS. PMID:16321805

  15. Circadian clock and pathology of the ageing brain

    PubMed Central

    Kondratova, A.A.; Kondratov, R.V.

    2013-01-01

    Ageing leads to functional deterioration of many brain systems, including the circadian clock - an internal time-keeping system that generates 24 hr rhythms in physiology and behaviour. Numerous clinical studies have established a direct correlation between the severity of neurodegenerative disorders, sleep disturbances and weakening of circadian clock functions. The latest data from model organisms, gene expression studies and clinical trials imply that the dysfunction of the circadian clock may contribute to the progression of ageing and age-associated pathologies, suggesting a functional link between the circadian clock, and age-associated decline of brain functions. Potential molecular mechanisms underlying this link include the circadian control of brain metabolism, reactive oxygen species homeostasis, hormone secretion, autophagy and stem cell proliferation. PMID:22395806

  16. Hearing Impairment Is Associated with Smaller Brain Volume in Aging

    PubMed Central

    Rigters, Stephanie C.; Bos, Daniel; Metselaar, Mick; Roshchupkin, Gennady V.; Baatenburg de Jong, Robert J.; Ikram, M. Arfan; Vernooij, Meike W.; Goedegebure, André

    2017-01-01

    Although recent studies show that age-related hearing impairment is associated with cerebral changes, data from a population perspective are still lacking. Therefore, we studied the relation between hearing impairment and brain volume in a large elderly cohort. From the population-based Rotterdam Study, 2,908 participants (mean age 65 years, 56% female) underwent a pure-tone audiogram to quantify hearing impairment. By performing MR imaging of the brain we quantified global and regional brain tissue volumes (total brain volume, gray matter volume, white matter (WM) volume, and lobe-specific volumes). We used multiple linear regression models, adjusting for age, sex, head size, time between hearing test and MR imaging, and relevant cognitive and cardiovascular covariates. Furthermore, we performed voxel-based morphometry to explore sub-regional differences. We found that a higher pure-tone threshold was associated with a smaller total brain volume [difference in standardized brain volume per decibel increase in hearing threshold in the age-sex adjusted model: -0.003 (95% confidence interval -0.004; -0.001)]. Specifically, WM volume was associated. Both associations were more pronounced in the lower frequencies. All associations were consistently present in all brain lobes in the lower frequencies and in most lobes in the higher frequencies, and were independent of cognitive function and cardiovascular risk factors. In voxel-based analyses we found associations of hearing impairment with smaller white volumes and some smaller and larger gray volumes, yet these were statistically non-significant. Our findings demonstrate that hearing impairment in elderly is related to smaller total brain volume, independent of cognition and cardiovascular risk factors. This mainly seems to be driven by smaller WM volume, throughout the brain. PMID:28163683

  17. Estimating the brain pathological age of Alzheimer’s disease patients from MR image data based on the separability distance criterion

    NASA Astrophysics Data System (ADS)

    Li, Yongming; Li, Fan; Wang, Pin; Zhu, Xueru; Liu, Shujun; Qiu, Mingguo; Zhang, Jingna; Zeng, Xiaoping

    2016-10-01

    Traditional age estimation methods are based on the same idea that uses the real age as the training label. However, these methods ignore that there is a deviation between the real age and the brain age due to accelerated brain aging. This paper considers this deviation and searches for it by maximizing the separability distance value rather than by minimizing the difference between the estimated brain age and the real age. Firstly, set the search range of the deviation as the deviation candidates according to prior knowledge. Secondly, use the support vector regression (SVR) as the age estimation model to minimize the difference between the estimated age and the real age plus deviation rather than the real age itself. Thirdly, design the fitness function based on the separability distance criterion. Fourthly, conduct age estimation on the validation dataset using the trained age estimation model, put the estimated age into the fitness function, and obtain the fitness value of the deviation candidate. Fifthly, repeat the iteration until all the deviation candidates are involved and get the optimal deviation with maximum fitness values. The real age plus the optimal deviation is taken as the brain pathological age. The experimental results showed that the separability was apparently improved. For normal control-Alzheimer’s disease (NC-AD), normal control-mild cognition impairment (NC-MCI), and MCI-AD, the average improvements were 0.178 (35.11%), 0.033 (14.47%), and 0.017 (39.53%), respectively. For NC-MCI-AD, the average improvement was 0.2287 (64.22%). The estimated brain pathological age could be not only more helpful to the classification of AD but also more precisely reflect accelerated brain aging. In conclusion, this paper offers a new method for brain age estimation that can distinguish different states of AD and can better reflect the extent of accelerated aging.

  18. Age, Plasticity, and Homeostasis In Childhood Brain Disorders

    PubMed Central

    Dennis, Maureen; Spiegler, Brenda J.; Juranek, Jenifer J.; Bigler, Erin D.; Snead, O. Carter; Fletcher, Jack M.

    2013-01-01

    It has been widely accepted that the younger the age and/or immaturity of the organism, the greater the brain plasticity, the young age plasticity privilege. This paper examines the relation of a young age to plasticity, reviewing human pediatric brain disorders, as well as selected animal models, human developmental and adult brain disorder studies. As well, we review developmental and childhood acquired disorders that involve a failure of regulatory homeostasis. Our core arguments are: Plasticity is neutral with respect to outcome. Although the effects of plasticity are often beneficial, the outcome of plasticity may be adaptive or maladaptive.The young age plasticity privilege has been overstated.Plastic change operates in concert with homeostatic mechanisms regulating change at every point in the lifespan.The same mechanisms that propel developmental change expose the immature brain to adverse events, making it more difficult for the immature than for the mature brain to sustain equilibrium between plasticity and homeostasis.Poor outcome in many neurodevelopmental disorders and childhood acquired brain insults is related to disequilibrium between plasticity and homeostasis. PMID:24096190

  19. Understanding How Exercise Promotes Cognitive Integrity in the Aging Brain.

    PubMed

    Laitman, Benjamin M; John, Gareth R

    2015-01-01

    Alterations in the structure and organization of the aging central nervous system (CNS), and associated functional deficits, result in cognitive decline and increase susceptibility to neurodegeneration. Age-related changes to the neurovascular unit (NVU), and their consequences for cerebrovascular function, are implicated as driving cognitive impairment during aging as well as in neurodegenerative disease. The molecular events underlying these effects are incompletely characterized. Similarly, the mechanisms underlying effects of factors that reduce the impact of aging on the brain, such as physical exercise, are also opaque. A study in this issue of PLOS Biology links the NVU to cognitive decline in the aging brain and suggests a potential underlying molecular mechanism. Notably, the study further links the protective effects of chronic exercise on cognition to neurovascular integrity during aging.

  20. The endocannabinoid system in normal and pathological brain ageing.

    PubMed

    Bilkei-Gorzo, Andras

    2012-12-05

    The role of endocannabinoids as inhibitory retrograde transmitters is now widely known and intensively studied. However, endocannabinoids also influence neuronal activity by exerting neuroprotective effects and regulating glial responses. This review centres around this less-studied area, focusing on the cellular and molecular mechanisms underlying the protective effect of the cannabinoid system in brain ageing. The progression of ageing is largely determined by the balance between detrimental, pro-ageing, largely stochastic processes, and the activity of the homeostatic defence system. Experimental evidence suggests that the cannabinoid system is part of the latter system. Cannabinoids as regulators of mitochondrial activity, as anti-oxidants and as modulators of clearance processes protect neurons on the molecular level. On the cellular level, the cannabinoid system regulates the expression of brain-derived neurotrophic factor and neurogenesis. Neuroinflammatory processes contributing to the progression of normal brain ageing and to the pathogenesis of neurodegenerative diseases are suppressed by cannabinoids, suggesting that they may also influence the ageing process on the system level. In good agreement with the hypothesized beneficial role of cannabinoid system activity against brain ageing, it was shown that animals lacking CB1 receptors show early onset of learning deficits associated with age-related histological and molecular changes. In preclinical models of neurodegenerative disorders, cannabinoids show beneficial effects, but the clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing.

  1. Linear accelerator radiosurgery in the management of brain tumours.

    PubMed

    Friedman, W A; Foote, K D

    2000-02-01

    Radiosurgery is an increasingly popular method for treating a variety of intracranial tumours. A great deal of treatment data has been accumulated suggesting that radiosurgery may be the treatment of choice for small acoustic schwannomas. Moreover, radiosurgery promises excellent tumour control and minimal risk in the treatment of small meningiomas in risky surgical locations such as the cavernous sinus. Radiosurgery offers superior local control rates for many metastatic neoplasms and has promise as an adjuvant 'boost' technique in certain malignant gliomas. This article presents a brief description of the linear accelerator, LINAC, radiosurgical technique, followed by a review of the more common applications of stereotactic radiosurgery in the treatment of intracranial neoplastic disease.

  2. Differential expression of sirtuins in the aging rat brain

    PubMed Central

    Braidy, Nady; Poljak, Anne; Grant, Ross; Jayasena, Tharusha; Mansour, Hussein; Chan-Ling, Tailoi; Smythe, George; Sachdev, Perminder; Guillemin, Gilles J.

    2015-01-01

    Although there are seven mammalian sirtuins (SIRT1-7), little is known about their expression in the aging brain. To characterize the change(s) in mRNA and protein expression of SIRT1-7 and their associated proteins in the brain of “physiologically” aged Wistar rats. We tested mRNA and protein expression levels of rat SIRT1-7, and the levels of associated proteins in the brain using RT-PCR and western blotting. Our data shows that SIRT1 expression increases with age, concurrently with increased acetylated p53 levels in all brain regions investigated. SIRT2 and FOXO3a protein levels increased only in the occipital lobe. SIRT3-5 expression declined significantly in the hippocampus and frontal lobe, associated with increases in superoxide and fatty acid oxidation levels, and acetylated CPS-1 protein expression, and a reduction in MnSOD level. While SIRT6 expression declines significantly with age acetylated H3K9 protein expression is increased throughout the brain. SIRT7 and Pol I protein expression increased in the frontal lobe. This study identifies previously unknown roles for sirtuins in regulating cellular homeostasis and healthy aging. PMID:26005404

  3. Comparing Aging and Fitness Effects on Brain Anatomy.

    PubMed

    Fletcher, Mark A; Low, Kathy A; Boyd, Rachel; Zimmerman, Benjamin; Gordon, Brian A; Tan, Chin H; Schneider-Garces, Nils; Sutton, Bradley P; Gratton, Gabriele; Fabiani, Monica

    2016-01-01

    Recent studies suggest that cardiorespiratory fitness (CRF) mitigates the brain's atrophy typically associated with aging, via a variety of beneficial mechanisms. One could argue that if CRF is generally counteracting the negative effects of aging, the same regions that display the greatest age-related volumetric loss should also show the largest beneficial effects of fitness. To test this hypothesis we examined structural MRI data from 54 healthy older adults (ages 55-87), to determine the overlap, across brain regions, of the profiles of age and fitness effects. Results showed that lower fitness and older age are associated with atrophy in several brain regions, replicating past studies. However, when the profiles of age and fitness effects were compared using a number of statistical approaches, the effects were not entirely overlapping. Interestingly, some of the regions that were most influenced by age were among those not influenced by fitness. Presumably, the age-related atrophy occurring in these regions is due to factors that are more impervious to the beneficial effects of fitness. Possible mechanisms supporting regional heterogeneity may include differential involvement in motor function, the presence of adult neurogenesis, and differential sensitivity to cerebrovascular, neurotrophic and metabolic factors.

  4. Berry Fruit Supplementation in the Aging Brain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The onset of age-related neurodegenerative diseases such as Alzheimer’s or Parkinson’s Disease, superimposed on a declining nervous system, could exacerbate the motor and cognitive behavioral deficits that normally occur in senescence. In cases of severe deficits in memory or motor function, hospit...

  5. Benefits from dietary polyphenols for brain aging and Alzheimer's disease.

    PubMed

    Rossi, L; Mazzitelli, S; Arciello, M; Capo, C R; Rotilio, G

    2008-12-01

    Brain aging and the most diffused neurodegenerative diseases of the elderly are characterized by oxidative damage, redox metals homeostasis impairment and inflammation. Food polyphenols can counteract these alterations in vitro and are therefore suggested to have potential anti-aging and brain-protective activities, as also indicated by the results of some epidemiological studies. Despite the huge and increasing amount of the in vitro studies trying to unravel the mechanisms of action of dietary polyphenols, the research in this field is still incomplete, and questions about bioavailability, biotransformation, synergism with other dietary factors, mechanisms of the antioxidant activity, risks inherent to their possible pro-oxidant activities are still unanswered. Most of all, the capacity of the majority of these compounds to cross the blood-brain barrier and reach brain is still unknown. This commentary discusses recent data on these aspects, particularly focusing on effects of curcumin, resveratrol and catechins on Alzheimer's disease.

  6. Associations between education and brain structure at age 73 years, adjusted for age 11 IQ

    PubMed Central

    Dickie, David Alexander; Ritchie, Stuart J.; Karama, Sherif; Pattie, Alison; Royle, Natalie A.; Corley, Janie; Aribisala, Benjamin S.; Valdés Hernández, Maria; Muñoz Maniega, Susana; Starr, John M.; Bastin, Mark E.; Evans, Alan C.; Wardlaw, Joanna M.; Deary, Ian J.

    2016-01-01

    Objective: To investigate how associations between education and brain structure in older age were affected by adjusting for IQ measured at age 11. Methods: We analyzed years of full-time education and measures from an MRI brain scan at age 73 in 617 community-dwelling adults born in 1936. In addition to average and vertex-wise cortical thickness, we measured total brain atrophy and white matter tract fractional anisotropy. Associations between brain structure and education were tested, covarying for sex and vascular health; a second model also covaried for age 11 IQ. Results: The significant relationship between education and average cortical thickness (β = 0.124, p = 0.004) was reduced by 23% when age 11 IQ was included (β = 0.096, p = 0.041). Initial associations between longer education and greater vertex-wise cortical thickness were significant in bilateral temporal, medial-frontal, parietal, sensory, and motor cortices. Accounting for childhood intelligence reduced the number of significant vertices by >90%; only bilateral anterior temporal associations remained. Neither education nor age 11 IQ was significantly associated with total brain atrophy or tract-averaged fractional anisotropy. Conclusions: The association between years of education and brain structure ≈60 years later was restricted to cortical thickness in this sample; however, the previously reported associations between longer education and a thicker cortex are likely to be overestimates in terms of both magnitude and distribution. This finding has implications for understanding, and possibly ameliorating, life-course brain health. PMID:27664981

  7. The Dopaminergic System in the Aging Brain of Drosophila

    PubMed Central

    White, Katherine E.; Humphrey, Dickon M.; Hirth, Frank

    2010-01-01

    Drosophila models of Parkinson's disease are characterized by two principal phenotypes: the specific loss of dopaminergic (DA) neurons in the aging brain and defects in motor behavior. However, an age-related analysis of these baseline parameters in wildtype Drosophila is lacking. Here we analyzed the DA system and motor behavior in aging Drosophila. DA neurons in the adult brain can be grouped into bilateral symmetric clusters, each comprising a stereotypical number of cells. Analysis of TH > mCD8::GFP and cell type-specific MARCM clones revealed that DA neurons show cluster-specific, stereotypical projection patterns with terminal arborization in target regions that represent distinct functional areas of the adult brain. Target areas include the mushroom bodies, involved in memory formation and motivation, and the central complex, involved in the control of motor behavior, indicating that similar to the mammalian brain, DA neurons in the fly brain are involved in the regulation of specific behaviors. Behavioral analysis revealed that Drosophila show an age-related decline in startle-induced locomotion and negative geotaxis. Motion tracking however, revealed that walking activity, and exploration behavior, but not centrophobism increase at late stages of life. Analysis of TH > Dcr2, mCD8::GFP revealed a specific effect of Dcr2 expression on walking activity but not on exploratory or centrophobic behavior, indicating that the siRNA pathway may modulate distinct DA behaviors in Drosophila. Moreover, DA neurons were maintained between early- and late life, as quantified by TH > mCD8::GFP and anti-TH labeling, indicating that adult onset, age-related degeneration of DA neurons does not occur in the aging brain of Drosophila. Taken together, our data establish baseline parameters in Drosophila for the study of Parkinson's disease as well as other disorders affecting DA neurons and movement control. PMID:21165178

  8. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging

    PubMed Central

    Bell, Robert D.; Winkler, Ethan A.; Sagare, Abhay P.; Singh, Itender; LaRue, Barb; Deane, Rashid; Zlokovic, Berislav V.

    2010-01-01

    SUMMARY Pericytes play a key role in the development of cerebral microcirculation. The exact role of pericytes in the neurovascular unit in the adult brain and during brain aging remains, however, elusive. Using adult viable pericyte-deficient mice, we show that pericyte loss leads to brain vascular damage by two parallel pathways: (1) reduction in brain microcirculation causing diminished brain capillary perfusion, cerebral blood flow and cerebral blood flow responses to brain activation which ultimately mediates chronic perfusion stress and hypoxia, and (2) blood-brain barrier breakdown associated with brain accumulation of serum proteins and several vasculotoxic and/or neurotoxic macromolecules ultimately leading to secondary neuronal degenerative changes. We show that age-dependent vascular damage in pericyte-deficient mice precedes neuronal degenerative changes, learning and memory impairment and the neuroinflammatory response. Thus, pericytes control key neurovascular functions that are necessary for proper neuronal structure and function, and pericytes loss results in a progressive age-dependent vascular-mediated neurodegeneration. PMID:21040844

  9. Experimental induction of type 2 diabetes in aging-accelerated mice triggered Alzheimer-like pathology and memory deficits.

    PubMed

    Mehla, Jogender; Chauhan, Balwantsinh C; Chauhan, Neelima B

    2014-01-01

    Alzheimer's disease (AD) is an age-dependent neurodegenerative disease constituting ~95% of late-onset non-familial/sporadic AD, and only ~5% accounting for early-onset familial AD. Availability of a pertinent model representing sporadic AD is essential for testing candidate therapies. Emerging evidence indicates a causal link between diabetes and AD. People with diabetes are >1.5-fold more likely to develop AD. Senescence-accelerated mouse model (SAMP8) of accelerated aging displays many features occurring early in AD. Given the role played by diabetes in the pre-disposition of AD, and the utility of SAMP8 non-transgenic mouse model of accelerated aging, we examined if high fat diet-induced experimental type 2 diabetes in SAMP8 mice will trigger pathological aging of the brain. Results showed that compared to non-diabetic SAMP8 mice, diabetic SAMP8 mice exhibited increased cerebral amyloid-β, dysregulated tau-phosphorylating glycogen synthase kinase 3β, reduced synaptophysin immunoreactivity, and displayed memory deficits, indicating Alzheimer-like changes. High fat diet-induced type 2 diabetic SAMP8 mice may represent the metabolic model of AD.

  10. A 64-channel 3T array coil for accelerated brain MRI

    PubMed Central

    Keil, Boris; Blau, James N.; Biber, Stephan; Hoecht, Philipp; Tountcheva, Veneta; Setsompop, Kawin; Triantafyllou, Christina; Wald, Lawrence L.

    2012-01-01

    A 64-channel brain array coil was developed and compared to a 32-channel array constructed with the same coil former geometry in order to precisely isolate the benefit of the two-fold increase in array coil elements. The constructed coils were developed for a standard clinical 3T MRI scanner and used a contoured head-shape curved former around the occipital pole and tapered in at the neck to both improve sensitivity and patient comfort. Additionally, the design is a compact, split-former design intended for robust daily use. Signal-to-noise ratio (SNR) and noise amplification (G-factor) for parallel imaging were quantitatively evaluated in human imaging and compared to a size and shape-matched 32-channel array coil. For unaccelerated imaging, the 64-channel array provided similar SNR in the brain center to the 32-channel array and 1.3-fold more SNR in the brain cortex. Reduced noise amplification during highly parallel imaging of the 64-channel array provided the ability to accelerate at approximately one unit higher at a given noise amplification compared to the sized-matched 32-channel array. For example, with a 4-fold acceleration rate, the central brain and cortical SNR of the 64-channel array was 1.2 and 1.4-fold higher, respectively, compared to the 32-channel array. The characteristics of the coil are demonstrated in accelerated brain imaging. PMID:22851312

  11. Aging of solidified/stabilized electrolytic manganese solid waste with accelerated carbonation and aging inhibition.

    PubMed

    Du, Bing; Zhou, Changbo; Dan, Zhigang; Zhao, Zhiyuan; Peng, Xianjia; Liu, Jianguo; Duan, Ning

    2016-12-01

    High concentrations of soluble Mn in electrolytic manganese solid waste (EMSW) in soil cause the severe contamination in China. Calcium oxide and magnesium oxide-dominated stabilizers are suitable for the solidification/stabilization (s/s) of EMSW. However, the long-term performance of s/s using those two types of stabilizer is problematic. The aim of this study was to develop an accelerated aging method to simulate the long-term natural carbonation of solidified/stabilized EMSW. The joint use of accelerated carbonation, leaching test, mineralogical analysis, and microstructural observation was applied to assess the long-term performance of the s/s EMSW system. On an accelerated carbonation test for solidified/stabilized EMSW, an increase in Mn leaching from 13.6 to 408 mg/kg and a 1.5-2.3 decrease in pH was achieved by using CaO-dominated stabilizers, while an increase in manganese (Mn) from 30 to 266 mg/kg and a decrease in pH of 0.17-0.68 was seen using MgO-dominated stabilizers. CaO+Na3PO4 and CaO+CaCO3 were exceptions in that the leaching value of soluble Mn was lower after carbonation. Mineralogical analysis showed that rhodochrosite in the carbonated s/s system was generated not only from the reduction of hausmannite but also from the reversible reaction between Mn(OH)2 and MnCO3. Carbonation destroyed the tight particle structure resulting in a porous and loose structure. As for s/s EMSW treated by MgO-dominated stabilizers, carbonation affected the agglomerating structure and mineralogical composition by increasing magnesium (Mg) migration, thereby forming hydromagnesite that had weak binding ability and a nested porous shape. Therefore, carbonation by itself does not cause deterioration to s/s products of the soluble Mn but does have significant effects on the microstructure and mineralogical composition. It is recommended to add Na3PO4 or CaCO3 into a single CaO stabilized EMSW system to prevent aging of the system, allow formation of Mn phosphate

  12. Comparison of mice with accelerated aging caused by distinct mechanisms

    PubMed Central

    Gurkar, Aditi U.; Niedernhofer, Laura J.

    2015-01-01

    Aging is the primary risk factor for numerous chronic, debilitating diseases. These diseases impact quality of life of the elderly and consume a large portion of health care costs. The cost of age-related diseases will only increase as the world's population continues to live longer. Thus it would be advantageous to consider aging itself as a therapeutic target, potentially stemming multiple age-related diseases simultaneously. While logical, this is extremely challenging as the molecular mechanisms that drive aging are still unknown. Furthermore, clinical trials to treat aging are impractical. Even in preclinical models, testing interventions to extend healthspan in old age is lengthy and therefore costly. One approach to expedite aging studies is to take advantage of mouse strains that are engineered to age rapidly. These strains are genetically and phenotypically quite diverse. This review aims to offer a comparison of several of these strains to highlight their relative strengths and weaknesses as models of mammalian and more specifically human aging. Additionally, careful identification of commonalities amongst the strains may lead to the identification of fundamental pathways of aging. PMID:25617508

  13. A Brain Network Processing the Age of Faces

    PubMed Central

    Homola, György A.; Jbabdi, Saad; Beckmann, Christian F.; Bartsch, Andreas J.

    2012-01-01

    Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke's understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships. PMID:23185334

  14. GPU-Accelerated Molecular Modeling Coming Of Age

    PubMed Central

    Stone, John E.; Hardy, David J.; Ufimtsev, Ivan S.

    2010-01-01

    Graphics processing units (GPUs) have traditionally been used in molecular modeling solely for visualization of molecular structures and animation of trajectories resulting from molecular dynamics simulations. Modern GPUs have evolved into fully programmable, massively parallel co-processors that can now be exploited to accelerate many scientific computations, typically providing about one order of magnitude speedup over CPU code and in special cases providing speedups of two orders of magnitude. This paper surveys the development of molecular modeling algorithms that leverage GPU computing, the advances already made and remaining issues to be resolved, and the continuing evolution of GPU technology that promises to become even more useful to molecular modeling. Hardware acceleration with commodity GPUs is expected to benefit the overall computational biology community by bringing teraflops performance to desktop workstations and in some cases potentially changing what were formerly batch-mode computational jobs into interactive tasks. PMID:20675161

  15. Life and death of neurons in the aging brain

    NASA Technical Reports Server (NTRS)

    Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)

    1997-01-01

    Neurodegenerative disorders are characterized by extensive neuron death that leads to functional decline, but the neurobiological correlates of functional decline in normal aging are less well defined. For decades, it has been a commonly held notion that widespread neuron death in the neocortex and hippocampus is an inevitable concomitant of brain aging, but recent quantitative studies suggest that neuron death is restricted in normal aging and unlikely to account for age-related impairment of neocortical and hippocampal functions. In this article, the qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored. When these data are viewed comprehensively, it appears that the primary neurobiological substrates for functional impairment in aging differ in important ways from those in neurodegenerative disorders such as Alzheimer's disease.

  16. Genetic mouse models of brain ageing and Alzheimer's disease.

    PubMed

    Bilkei-Gorzo, Andras

    2014-05-01

    Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed.

  17. Comparing Aging and Fitness Effects on Brain Anatomy

    PubMed Central

    Fletcher, Mark A.; Low, Kathy A.; Boyd, Rachel; Zimmerman, Benjamin; Gordon, Brian A.; Tan, Chin H.; Schneider-Garces, Nils; Sutton, Bradley P.; Gratton, Gabriele; Fabiani, Monica

    2016-01-01

    Recent studies suggest that cardiorespiratory fitness (CRF) mitigates the brain’s atrophy typically associated with aging, via a variety of beneficial mechanisms. One could argue that if CRF is generally counteracting the negative effects of aging, the same regions that display the greatest age-related volumetric loss should also show the largest beneficial effects of fitness. To test this hypothesis we examined structural MRI data from 54 healthy older adults (ages 55–87), to determine the overlap, across brain regions, of the profiles of age and fitness effects. Results showed that lower fitness and older age are associated with atrophy in several brain regions, replicating past studies. However, when the profiles of age and fitness effects were compared using a number of statistical approaches, the effects were not entirely overlapping. Interestingly, some of the regions that were most influenced by age were among those not influenced by fitness. Presumably, the age-related atrophy occurring in these regions is due to factors that are more impervious to the beneficial effects of fitness. Possible mechanisms supporting regional heterogeneity may include differential involvement in motor function, the presence of adult neurogenesis, and differential sensitivity to cerebrovascular, neurotrophic and metabolic factors. PMID:27445740

  18. Evolution of the Aging Brain Transcriptome and Synaptic Regulation

    PubMed Central

    Dakin, Kelly A.; Vann, James M.; Isaacs, Adrian; Geula, Chengiz; Wang, Jianbin; Pan, Ying; Gabuzda, Dana H.; Li, Cheng; Prolla, Tomas A.; Yankner, Bruce A.

    2008-01-01

    Alzheimer's disease and other neurodegenerative disorders of aging are characterized by clinical and pathological features that are relatively specific to humans. To obtain greater insight into how brain aging has evolved, we compared age-related gene expression changes in the cortex of humans, rhesus macaques, and mice on a genome-wide scale. A small subset of gene expression changes are conserved in all three species, including robust age-dependent upregulation of the neuroprotective gene apolipoprotein D (APOD) and downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent protein kinase IV (CAMK4). However, analysis of gene ontology and cell type localization shows that humans and rhesus macaques have diverged from mice due to a dramatic increase in age-dependent repression of neuronal genes. Many of these age-regulated neuronal genes are associated with synaptic function. Notably, genes associated with GABA-ergic inhibitory function are robustly age-downregulated in humans but not in mice at the level of both mRNA and protein. Gene downregulation was not associated with overall neuronal or synaptic loss. Thus, repression of neuronal gene expression is a prominent and recently evolved feature of brain aging in humans and rhesus macaques that may alter neural networks and contribute to age-related cognitive changes. PMID:18830410

  19. Improved measurement of brain deformation during mild head acceleration using a novel tagged MRI sequence.

    PubMed

    Knutsen, Andrew K; Magrath, Elizabeth; McEntee, Julie E; Xing, Fangxu; Prince, Jerry L; Bayly, Philip V; Butman, John A; Pham, Dzung L

    2014-11-07

    In vivo measurements of human brain deformation during mild acceleration are needed to help validate computational models of traumatic brain injury and to understand the factors that govern the mechanical response of the brain. Tagged magnetic resonance imaging is a powerful, noninvasive technique to track tissue motion in vivo which has been used to quantify brain deformation in live human subjects. However, these prior studies required from 72 to 144 head rotations to generate deformation data for a single image slice, precluding its use to investigate the entire brain in a single subject. Here, a novel method is introduced that significantly reduces temporal variability in the acquisition and improves the accuracy of displacement estimates. Optimization of the acquisition parameters in a gelatin phantom and three human subjects leads to a reduction in the number of rotations from 72 to 144 to as few as 8 for a single image slice. The ability to estimate accurate, well-resolved, fields of displacement and strain in far fewer repetitions will enable comprehensive studies of acceleration-induced deformation throughout the human brain in vivo.

  20. Manifold learning on brain functional networks in aging.

    PubMed

    Qiu, Anqi; Lee, Annie; Tan, Mingzhen; Chung, Moo K

    2015-02-01

    We propose a new analysis framework to utilize the full information of brain functional networks for computing the mean of a set of brain functional networks and embedding brain functional networks into a low-dimensional space in which traditional regression and classification analyses can be easily employed. For this, we first represent the brain functional network by a symmetric positive matrix computed using sparse inverse covariance estimation. We then impose a Log-Euclidean Riemannian manifold structure on brain functional networks whose norm gives a convenient and practical way to define a mean. Finally, based on the fact that the computation of linear operations can be done in the tangent space of this Riemannian manifold, we adopt Locally Linear Embedding (LLE) to the Log-Euclidean Riemannian manifold space in order to embed the brain functional networks into a low-dimensional space. We show that the integration of the Log-Euclidean manifold with LLE provides more efficient and succinct representation of the functional network and facilitates regression analysis, such as ridge regression, on the brain functional network to more accurately predict age when compared to that of the Euclidean space of functional networks with LLE. Interestingly, using the Log-Euclidean analysis framework, we demonstrate the integration and segregation of cortical-subcortical networks as well as among the salience, executive, and emotional networks across lifespan.

  1. Acetyl-L-carnitine improves aged brain function.

    PubMed

    Kobayashi, Satoru; Iwamoto, Machiko; Kon, Kazuo; Waki, Hatsue; Ando, Susumu; Tanaka, Yasukazu

    2010-07-01

    The effects of acetyl-L-carnitine (ALCAR), an acetyl derivative of L-carnitine, on memory and learning capacity and on brain synaptic functions of aged rats were examined. Male Fischer 344 rats were given ALCAR (100 mg/kg bodyweight) per os for 3 months and were subjected to the Hebb-Williams tasks and AKON-1 task to assess their learning capacity. Cholinergic activities were determined with synaptosomes isolated from brain cortices of the rats. Choline parameters, the high-affinity choline uptake, acetylcholine (ACh) synthesis and depolarization-evoked ACh release were all enhanced in the ALCAR group. An increment of depolarization-induced calcium ion influx into synaptosomes was also evident in rats given ALCAR. Electrophysiological studies using hippocampus slices indicated that the excitatory postsynaptic potential slope and population spike size were both increased in ALCAR-treated rats. These results indicate that ALCAR increases synaptic neurotransmission in the brain and consequently improves learning capacity in aging rats.

  2. DNA Strand Breaks, Neurodegeneration and Aging in the Brain

    PubMed Central

    Katyal, Sachin; McKinnon, Peter J.

    2013-01-01

    Defective responses to DNA single- or double-strand breaks can result in neurological disease, underscoring the critical importance of DNA repair for neural homeostasis. Human DNA repair-deficient syndromes are generally congenital, in which brain pathology reflects the consequences of developmentally incurred DNA damage. Although, it is unclear to what degree DNA strand-break repair defects in mature neural cells contributes to disease pathology. However, DNA single-strand breaks are a relatively common lesion which if not repaired can impact cells via interference with transcription. Thus, this lesion, and probably to a lesser extent DNA double strand breaks, may be particularly relevant to aging in the neural cell population. In this review we will examine the consequences of defective DNA strand break repair towards homeostasis in the brain. Further, we also consider the utility of mouse models as reagents to understand the connection between DNA strand breaks and aging in the brain. PMID:18455751

  3. Brain surgery breathes new life into aging plants

    SciTech Connect

    Makansi, J.

    2006-04-15

    Unlike managing the human aging process, extending the life of a power plant often includes brain surgery, modernizing its control and automation system. Lately, such retrofits range from wholesale replacing of existing controls to the addition of specific control elements that help optimize performance. Pending revisions to safety codes and cybersecurity issues also need to be considered. 4 figs.

  4. Neuroimaging of Cerebrovascular Disease in the Aging Brain

    PubMed Central

    Gupta, Ajay; Nair, Sreejit; Schweitzer, Andrew D.; Kishore, Sirish; Johnson, Carl E.; Comunale, Joseph P.; Tsiouris, Apostolos J.; Sanelli, Pina C.

    2012-01-01

    Cerebrovascular disease remains a significant public health burden with its greatest impact on the elderly population. Advances in neuroimaging techniques allow detailed and sophisticated evaluation of many manifestations of cerebrovascular disease in the brain parenchyma as well as in the intracranial and extracranial vasculature. These tools continue to contribute to our understanding of the multifactorial processes that occur in the age-dependent development of cerebrovascular disease. Structural abnormalities related to vascular disease in the brain and vessels have been well characterized with CT and MRI based techniques. We review some of the pathophysiologic mechanisms in the aging brain and cerebral vasculature and the related structural abnormalities detectable on neuroimaging, including evaluation of age-related white matter changes, atherosclerosis of the cerebral vasculature, and cerebral infarction. In addition, newer neuroimaging techniques, such as diffusion tensor imaging, perfusion techniques, and assessment of cerebrovascular reserve, are also reviewed, as these techniques can detect physiologic alterations which complement the morphologic changes that cause cerebrovascular disease in the aging brain.Further investigation of these advanced imaging techniques has potential application to the understanding and diagnosis of cerebrovascular disease in the elderly. PMID:23185721

  5. Brain-Based Teaching in the Digital Age

    ERIC Educational Resources Information Center

    Sprenger, Marilee

    2010-01-01

    In the digital age, your students have the ways, means, and speed to gather any information they want. But they need your guidance more than ever. Discover how digital technology is actually changing your students' brains. Learn why this creates new obstacles for teachers, but also opens up potential new pathways for learning. You will understand…

  6. Alpha oscillatory correlates of motor inhibition in the aged brain

    PubMed Central

    Bönstrup, Marlene; Hagemann, Julian; Gerloff, Christian; Sauseng, Paul; Hummel, Friedhelm C.

    2015-01-01

    Exerting inhibitory control is a cognitive ability mediated by functions known to decline with age. The goal of this study is to add to the mechanistic understanding of cortical inhibition during motor control in aged brains. Based on behavioral findings of impaired inhibitory control with age we hypothesized that elderly will show a reduced or a lack of EEG alpha-power increase during tasks that require motor inhibition. Since inhibitory control over movements has been shown to rely on prior motor memory formation, we investigated cortical inhibitory processes at two points in time—early after learning and after an overnight consolidation phase and hypothesized an overnight increase of inhibitory capacities. Young and elderly participants acquired a complex finger movement sequence and in each experimental session brain activity during execution and inhibition of the sequence was recorded with multi-channel EEG. We assessed cortical processes of sustained inhibition by means of task-induced changes of alpha oscillatory power. During inhibition of the learned movement, young participants showed a significant alpha power increase at the sensorimotor cortices whereas elderly did not. Interestingly, for both groups, the overnight consolidation phase improved up-regulation of alpha power during sustained inhibition. This points to deficits in the generation and enhancement of local inhibitory mechanisms at the sensorimotor cortices in aged brains. However, the alpha power increase in both groups implies neuroplastic changes that strengthen the network of alpha power generation over time in young as well as elderly brains. PMID:26528179

  7. Correlation between mechanical and chemical degradation after outdoor and accelerated laboratory aging for multilayer photovoltaic backsheets

    NASA Astrophysics Data System (ADS)

    Lin, Chiao-Chi; Lyu, Yadong; Yu, Li-Chieh; Gu, Xiaohong

    2016-09-01

    Channel cracking fragmentation testing and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy were utilized to study mechanical and chemical degradation of a multilayered backsheet after outdoor and accelerated laboratory aging. A model sample of commercial PPE backsheet, namely polyethylene terephthalate/polyethylene terephthalate/ethylene vinyl acetate (PET/PET/EVA) was investigated. Outdoor aging was performed in Gaithersburg, Maryland, USA for up to 510 days, and complementary accelerated laboratory aging was conducted on the NIST (National Institute of Standards and Technology) SPHERE (Simulated Photodegradation via High Energy Radiant Exposure). Fracture energy, mode I stress intensity factor and film strength were analyzed using an analytical model based on channel cracking fragmentation testing results. The correlation between mechanical and chemical degradation was discussed for both outdoor and accelerated laboratory aging. The results of this work provide preliminary understanding on failure mechanism of backsheets after weathering, laying the groundwork for linking outdoor and indoor accelerated laboratory testing for multilayer photovoltaic backsheets.

  8. Aging Effects on Regional Brain Structural Changes in Schizophrenia

    PubMed Central

    Nenadić, Igor; Sauer, Heinrich; Smesny, Stefan; Gaser, Christian

    2012-01-01

    Background: Although mostly conceptualized as a neurodevelopmental disorder, there is an increasing interest in progressive changes of cognitive deficits and brain structure and function in schizophrenia across the life span. Methods: In this study, we investigated age-related changes in regional gray matter using voxel-based morphometry in a sample of 99 patients (age range 18–65 years) with Diagnostic and Statistical Manual of Mental Disorders-IV schizophrenia and 113 healthy controls (age range 19–59 years) using a cross-sectional design. Results: We found steeper age-related decline in gray matter in patients in a cluster comprising the left superior temporal cortex and adjacent inferior parietal lobule. We then divided the schizophrenia sample in 3 subgroups based on a 3-factor model of psychopathology ratings. Age-related changes were markedly different in each of the 3 subgroups (compared with healthy controls). While patients with predominantly paranoid symptoms showed stronger age-related progression in the left superior temporal cortex and right inferior frontal gyrus, those of the disorganized subgroup had stronger gray matter loss in the left lateral cerebellum, while the predominantly negative subgroup showed minor effects in the left superior temporal gyrus. Conclusions: Our findings show that differences in brain structural changes associated with aging diverge between schizophrenia patients and healthy subjects and that different subgroups within a patient sample might be at higher risk of age-related regional gray matter loss. PMID:21296908

  9. Aging and Gene Expression in the Primate Brain

    SciTech Connect

    Fraser, Hunter B.; Khaitovich, Philipp; Plotkin, Joshua B.; Paabo, Svante; Eisen, Michael B.

    2005-02-18

    It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.

  10. Brain development and aging: Overlapping and unique patterns of change

    PubMed Central

    Tamnes, Christian K.; Walhovd, Kristine B.; Dale, Anders M.; Østby, Ylva; Grydeland, Håkon; Richardson, George; Westlye, Lars T.; Roddey, J. Cooper; Hagler, Donald J.; Due-Tønnessen, Paulina; Holland, Dominic; Fjell, Anders M.

    2017-01-01

    Early-life development is characterized by dramatic changes, impacting lifespan function more than changes inany other period. Developmental origins of neurocognitive late-life functions are acknowledged, but detailed longitudinal magnetic resonance imaging studies of brain maturation and direct comparisons with aging are lacking. To these aims, a novel method was used to measure longitudinal volume changes in development (n = 85, 8–22 years) and aging (n = 142, 60–91 years). Developmental reductions exceeded 1% annually in much of cortex, more than double that seen in aging, with a posterior-to-anterior gradient. Cortical reductions were greater than subcortical during development, while the opposite held in aging. The pattern of lateral cortical changes was similar across development and aging, but the pronounced medial temporal reduction in aging was not precast in development. Converging patterns of change in adolescents and elderly, particularly in medial prefrontal areas, suggest that late developed cortices are especially vulnerable to atrophy in aging. A key question in future research will be to disentangle the neurobiological underpinnings for the differences and the similarities between brain changes in development and aging. PMID:23246860

  11. Changes in expressions of proinflammatory cytokines IL-1beta, TNF-alpha and IL-6 in the brain of senescence accelerated mouse (SAM) P8.

    PubMed

    Tha, K K; Okuma, Y; Miyazaki, H; Murayama, T; Uehara, T; Hatakeyama, R; Hayashi, Y; Nomura, Y

    2000-12-01

    The senescence-accelerated mouse (SAM) is known to be a murine model for accelerated aging. The SAMP8 strain shows age-related deterioration of learning and memory at an earlier age than control mice (SAMR1). In the present study, we investigated the changes in expressions of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the brain of SAMP8. In the hippocampus of 10 months old SAMP8, the expression of IL-1 mRNA was significantly elevated in comparison with that of SAMR1. In both strains of SAMs, increases in IL-1beta protein in the brain were observed at 10 months of age compared with 2 and 5 months. The only differences found between the strain in protein levels were at 10 months and were elevations in IL-1beta in the hippocampus and hypothalamus, and in TNF-alpha and IL-6 in the cerebral cortex and the hippocampus in SAMP8 as compared with SAMR1. However, lipopolysaccharide-induced increases in the expression of these cytokines in brain did not differ between SAMP8 and SAMR1. Increases in expression of proinflammatory cytokines in the brain may be involved in the age-related neural dysfunction and/or learning deficiency in SAMP8.

  12. Age prediction on the basis of brain anatomical measures.

    PubMed

    Valizadeh, S A; Hänggi, J; Mérillat, S; Jäncke, L

    2017-02-01

    In this study, we examined whether age can be predicted on the basis of different anatomical features obtained from a large sample of healthy subjects (n = 3,144). From this sample we obtained different anatomical feature sets: (1) 11 larger brain regions (including cortical volume, thickness, area, subcortical volume, cerebellar volume, etc.), (2) 148 cortical compartmental thickness measures, (3) 148 cortical compartmental area measures, (4) 148 cortical compartmental volume measures, and (5) a combination of the above-mentioned measures. With these anatomical feature sets, we predicted age using 6 statistical techniques (multiple linear regression, ridge regression, neural network, k-nearest neighbourhood, support vector machine, and random forest). We obtained very good age prediction accuracies, with the highest accuracy being R(2)  = 0.84 (prediction on the basis of a neural network and support vector machine approaches for the entire data set) and the lowest being R(2)  = 0.40 (prediction on the basis of a k-nearest neighborhood for cortical surface measures). Interestingly, the easy-to-calculate multiple linear regression approach with the 11 large brain compartments resulted in a very good prediction accuracy (R(2)  = 0.73), whereas the application of the neural network approach for this data set revealed very good age prediction accuracy (R(2)  = 0.83). Taken together, these results demonstrate that age can be predicted well on the basis of anatomical measures. The neural network approach turned out to be the approach with the best results. In addition, it was evident that good prediction accuracies can be achieved using a small but nevertheless age-representative dataset of brain features. Hum Brain Mapp 38:997-1008, 2017. © 2016 Wiley Periodicals, Inc.

  13. Transcriptomics of Post-Stroke Angiogenesis in the Aged Brain

    PubMed Central

    Buga, Ana Maria; Margaritescu, Claudiu; Scholz, Claus Juergen; Radu, Eugen; Zelenak, Christine; Popa-Wagner, Aurel

    2014-01-01

    Despite the obvious clinical significance of post-stroke angiogenesis in aged subjects, a detailed transcriptomic analysis of post-stroke angiogenesis has not yet been undertaken in an aged experimental model. In this study, by combining stroke transcriptomics with immunohistochemistry in aged rats and post-stroke patients, we sought to identify an age-specific gene expression pattern that may characterize the angiogenic process after stroke. We found that both young and old infarcted rats initiated vigorous angiogenesis. However, the young rats had a higher vascular density by day 14 post-stroke. “New-for-stroke” genes that were linked to the increased vasculature density in young animals included Angpt2, Angptl2, Angptl4, Cib1, Ccr2, Col4a2, Cxcl1, Lef1, Hhex, Lamc1, Nid2, Pcam1, Plod2, Runx3, Scpep1, S100a4, Tgfbi, and Wnt4, which are required for sprouting angiogenesis, reconstruction of the basal lamina (BL), and the resolution phase. The vast majority of genes involved in sprouting angiogenesis (Angpt2, Angptl4, Cib1, Col8a1, Nrp1, Pcam1, Pttg1ip, Rac2, Runx1, Tnp4, Wnt4); reconstruction of a new BL (Col4a2, Lamc1, Plod2); or tube formation and maturation (Angpt1, Gpc3, Igfbp7, Sparc, Tie2, Tnfsf10), had however, a delayed upregulation in the aged rats. The angiogenic response in aged rats was further diminished by the persistent upregulation of “inflammatory” genes (Cxcl12, Mmp8, Mmp12, Mmp14, Mpeg1, Tnfrsf1a, Tnfrsf1b) and vigorous expression of genes required for the buildup of the fibrotic scar (Cthrc1, Il6ra, Il13ar1, Il18, Mmp2, Rassf4, Tgfb1, Tgfbr2, Timp1). Beyond this barrier, angiogenesis in the aged brains was similar to that in young brains. We also found that the aged human brain is capable of mounting a vigorous angiogenic response after stroke, which most likely reflects the remaining brain plasticity of the aged brain. PMID:24672479

  14. Epigenetic Determinants of Healthy and Diseased Brain Aging and Cognition

    PubMed Central

    S., Akbarian; S., Beeri M.; V., Haroutunian

    2014-01-01

    A better understanding of normal and diseased brain aging and cognition will have a significant public health impact, given that the oldest-old persons over 85 years of age represent the fastest growing segment in the population in developed countries, with over 30 million new cases of dementia predicted to occur world-wide each year by 2040. Dysregulation of gene expression, and more generally, genome organization and function, is thought to contribute to age-related declines in cognition. Remarkably, nearly all neuronal nuclei that reside in an aged brain had permanently exited from the cell cycle during prenatal development, and DNA methylation and histone modifications and other molecular constituents of the epigenome are likely to play a critical role in the maintenance of neuronal health and function throughout the entire lifespan. Here, we provide an overview on age-related changes in the brain’s chromatin structures, highlight potential epigenetic drug targets for cognitive decline and age-related neurodegenerative disease and discuss opportunities and challenges when studying ‘epigenetic biomarkers’ in aging research. PMID:23571692

  15. Maladaptive autonomic regulation in PTSD accelerates physiological aging

    PubMed Central

    Williamson, John B.; Porges, Eric C.; Lamb, Damon G.; Porges, Stephen W.

    2015-01-01

    A core manifestation of post-traumatic stress disorder (PTSD) is a disconnection between physiological state and psychological or behavioral processes necessary to adequately respond to environmental demands. Patients with PTSD experience abnormal oscillations in autonomic states supporting either fight and flight behaviors or withdrawal, immobilization, and dissociation without an intervening “calm” state that would provide opportunities for positive social interactions. This defensive autonomic disposition is adaptive in dangerous and life threatening situations, but in the context of every-day life may lead to significant psychosocial distress and deteriorating social relationships. The perpetuation of these maladaptive autonomic responses may contribute to the development of comorbid mental health issues such as depression, loneliness, and hostility that further modify the nature of cardiovascular behavior in the context of internal and external stressors. Over time, changes in autonomic, endocrine, and immune function contribute to deteriorating health, which is potently expressed in brain dysfunction and cardiovascular disease. In this theoretical review paper, we present an overview of the literature on the chronic health effects of PTSD. We discuss the brain networks underlying PTSD in the context of autonomic efferent and afferent contributions and how disruption of these networks leads to poor health outcomes. Finally, we discuss treatment approaches based on our theoretical model of PTSD. PMID:25653631

  16. Accelerated delimitation of the infarct zone by capillary-derived nestin-positive cells in aged rats.

    PubMed

    Popa-Wagner, Aurel; Dinca, Ivona; Yalikun, Suofu; Walker, Lary; Kroemer, Heyo; Kessler, Christof

    2006-02-01

    brain has the capability to mount a cytoproliferative response to injury, but the timing of the cellular and genetic reaction to cerebral insult is accelerated in aged animals; (ii) the proliferating cells contribute to the formation of the glial scar, but few of the cells appear to become neurons; and (iii) the vasculature plays a hitherto unrecognized role as a source of proliferating cells after stroke. Because capillary-derived cells help to form the glial scar, elucidating the molecular basis of this phenomenon and its acceleration in the aging brain could yield novel approaches to enhancing neurorestoration in the elderly.

  17. Accelerated retinal aging in PACAP knock-out mice.

    PubMed

    Kovács-Valasek, Andrea; Szabadfi, Krisztina; Dénes, Viktória; Szalontai, Bálint; Tamás, Andrea; Kiss, Péter; Szabó, Aliz; Setalo, Gyorgy; Reglődi, Dóra; Gábriel, Robert

    2017-02-13

    Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophic and neuroprotective peptide. PACAP and its receptors are widely distributed in the retina. A number of reports provided evidence that PACAP is neuroprotective in retinal degenerations. The current study compared retina cell type-specific differences in young (3-4months) and aged adults (14-16months), of wild-type (WT) mice and knock-out (KO) mice lacking endogenous PACAP production during the course of aging. Histological, immunocytochemical and Western blot examinations were performed. The staining for standard neurochemical markers (tyrosine hydroxylase for dopaminergic cells, calbindin 28 kDa for horizontal cells, protein kinase Cα for rod bipolar cells) of young adult PACAP KO retinas showed no substantial alterations compared to young adult WT retinas, except for the specific PACAP receptor (PAC1-R) staining. We could not detect PAC1-R immunoreactivity in bipolar and horizontal cells in young adult PACAP KO animals. Some other age-related changes were observed only in the PACAP KO mice only. These alterations included horizontal and rod bipolar cell dendritic sprouting into the photoreceptor layer and decreased ganglion cell number. Also, Müller glial cells showed elevated GFAP expression compared to the aging WT retinas. Furthermore, Western blot analyses revealed significant differences between the phosphorylation state of ERK1/2 and JNK in KO mice, indicating alterations in the MAPK signaling pathway. These results support the conclusion that endogenous PACAP contributes to protection against aging of the nervous system.

  18. Indestructible plastic: the neuroscience of the new aging brain.

    PubMed

    Holman, Constance; de Villers-Sidani, Etienne

    2014-01-01

    In recent years, research on experience-dependent plasticity has provided valuable insight on adaptation to environmental input across the lifespan, and advances in understanding the minute cellular changes underlying the brain's capacity for self-reorganization have opened exciting new possibilities for treating illness and injury. Ongoing work in this line of inquiry has also come to deeply influence another field: cognitive neuroscience of the normal aging. This complex process, once considered inevitable or beyond the reach of treatment, has been transformed into an arena of intense investigation and strategic intervention. However, important questions remain about this characterization of the aging brain, and the assumptions it makes about the social, cultural, and biological space occupied by cognition in the older individual and body. The following paper will provide a critical examination of the move from basic experiments on the neurophysiology of experience-dependent plasticity to the growing market for (and public conception of) cognitive aging as a medicalized space for intervention by neuroscience-backed technologies. Entangled with changing concepts of normality, pathology, and self-preservation, we will argue that this new understanding, led by personalized cognitive training strategies, is approaching a point where interdisciplinary research is crucial to provide a holistic and nuanced understanding of the aging process. This new outlook will allow us to move forward in a space where our knowledge, like our new conception of the brain, is never static.

  19. Low intensity laser therapy accelerates muscle regeneration in aged rats

    PubMed Central

    Vatansever, Fatma; Rodrigues, Natalia C.; Assis, Livia L.; Peviani, Sabrina S.; Durigan, Joao L.; Moreira, Fernando M.A.; Hamblin, Michael R.; Parizotto, Nivaldo A.

    2013-01-01

    Background Elderly people suffer from skeletal muscle disorders that undermine their daily activity and quality of life; some of these problems can be listed as but not limited to: sarcopenia, changes in central and peripheral nervous system, blood hypoperfusion, regenerative changes contributing to atrophy, and muscle weakness. Determination, proliferation and differentiation of satellite cells in the regenerative process are regulated by specific transcription factors, known as myogenic regulatory factors (MRFs). In the elderly, the activation of MRFs is inefficient which hampers the regenerative process. Recent studies found that low intensity laser therapy (LILT) has a stimulatory effect in the muscle regeneration process. However, the effects of this therapy when associated with aging are still unknown. Objective This study aimed to evaluate the effects of LILT (λ=830 nm) on the tibialis anterior (TA) muscle of aged rats. Subjects and methods The total of 56 male Wistar rats formed two population sets: old and young, with 28 animals in each set. Each of these sets were randomly divided into four groups of young rats (3 months of age) with n=7 per group and four groups of aged rats (10 months of age) with n=7 per group. These groups were submitted to cryoinjury + laser irradiation, cryoinjury only, laser irradiation only and the control group (no cryoinjury/no laser irradiation). The laser treatment was performed for 5 consecutive days. The first laser application was done 24 h after the injury (on day 2) and on the seventh day, the TA muscle was dissected and removed under anesthesia. After this the animals were euthanized. Histological analyses with toluidine blue as well as hematoxylin-eosin staining (for counting the blood capillaries) were performed for the lesion areas. In addition, MyoD and VEGF mRNA was assessed by quantitative polymerase chain reaction. Results The results showed significant elevation (p<0.05) in MyoD and VEGF genes expression levels

  20. A cord blood monocyte–derived cell therapy product accelerates brain remyelination

    PubMed Central

    Buntz, Susan; Scotland, Paula; Xu, Li; Noeldner, Pamela; Patel, Sachit; Wollish, Amy; Gunaratne, Aruni; Gentry, Tracy; Matsushima, Glenn K.; Kurtzberg, Joanne; Balber, Andrew E.

    2016-01-01

    Microglia and monocytes play important roles in regulating brain remyelination. We developed DUOC-01, a cell therapy product intended for treatment of demyelinating diseases, from banked human umbilical cord blood (CB) mononuclear cells. Immunodepletion and selection studies demonstrated that DUOC-01 cells are derived from CB CD14+ monocytes. We compared the ability of freshly isolated CB CD14+ monocytes and DUOC-01 cells to accelerate remyelination of the brains of NOD/SCID/IL2Rγnull mice following cuprizone feeding–mediated demyelination. The corpus callosum of mice intracranially injected with DUOC-01 showed enhanced myelination, a higher proportion of fully myelinated axons, decreased gliosis and cellular infiltration, and more proliferating oligodendrocyte lineage cells than those of mice receiving excipient. Uncultured CB CD14+ monocytes also accelerated remyelination, but to a significantly lesser extent than DUOC-01 cells. Microarray analysis, quantitative PCR studies, Western blotting, and flow cytometry demonstrated that expression of factors that promote remyelination including PDGF-AA, stem cell factor, IGF1, MMP9, MMP12, and triggering receptor expressed on myeloid cells 2 were upregulated in DUOC-01 compared to CB CD14+ monocytes. Collectively, our results show that DUOC-01 accelerates brain remyelination by multiple mechanisms and could be beneficial in treating demyelinating conditions. PMID:27699230

  1. Accelerated ageing in testing bricks used in the conservation of historic buildings

    NASA Astrophysics Data System (ADS)

    Pavlendová, Gabriela; Podoba, Rudolf; Baník, Ivan

    2014-11-01

    The effect of accelerated climate ageing on historical bricks in the laboratory is investigated in the paper. Differences in thermal properties are experimentally determined and studied before and after bricks exposure to climate ageing, which consists of 60 freeze-thaw cycles. For measuring thermal conductivity, diffusivity and specific heat, pulse method is used.

  2. Traumatic stress, oxidative stress and posttraumatic stress disorder: neurodegeneration and the accelerated-aging hypothesis

    PubMed Central

    Miller, Mark W.; Sadeh, Naomi

    2014-01-01

    Posttraumatic stress disorder (PTSD) is associated with elevated risk for a variety of age-related diseases and neurodegeneration. In this paper, we review evidence relevant to the hypothesis that chronic PTSD constitutes a form of persistent life stress that potentiates oxidative stress (OXS) and accelerates cellular aging. We provide an overview of empirical studies that have examined the effects of psychological stress on OXS, discuss the stress-perpetuating characteristics of PTSD, and then identify mechanisms by which PTSD might promote OXS and accelerated aging. We review studies on OXS-related genes and the role that they may play in moderating the effects of PTSD on neural integrity and conclude with a discussion of directions for future research on antioxidant treatments and biomarkers of accelerated aging in PTSD. PMID:25245500

  3. New cellular and molecular approaches to ageing brain.

    PubMed

    Tripathi, Anurag

    2012-10-01

    The last decade has witnessed a mammoth progress in the area of brain ageing. Recent gene profiling and brain imaging techniques have made it possible to explore the dark areas of ageing neurons in a new molecular perspective. Many conserved pathways and cellular and molecular mechanisms particularly nuclear mitochondrial molecular interactions are known now. Disruptions in mitochondrial function and reduction in cellular antioxidative and immunoproteins contribute to generation of reactive oxygen species (ROS) which leads to deteriorated adult neurogenesis, reduced white matter and compromised neural plasticity. The overall deteriorated structure and function of neurons is manifested in form of cognitive decline and prolonged neurodegenerative disorders. Dietary restrictions (DR), physical and mental activities however have been shown to counter these ailments. However more precise molecular dynamics at protein levels is still debatable which is the future task for neuroscientists.

  4. Lucid dreaming: an age-dependent brain dissociation.

    PubMed

    Voss, Ursula; Frenzel, Clemens; Koppehele-Gossel, Judith; Hobson, Allan

    2012-12-01

    The current study focused on the distribution of lucid dreams in school children and young adults. The survey was conducted on a large sample of students aged 6-19 years. Questions distinguished between past and current experience with lucid dreams. Results suggest that lucid dreaming is quite pronounced in young children, its incidence rate drops at about age 16 years. Increased lucidity was found in those attending higher level compared with lower level schools. Taking methodological issues into account, we feel confident to propose a link between the natural occurrence of lucid dreaming and brain maturation.

  5. Primate aging in the mammalian scheme: the puzzle of extreme variation in brain aging.

    PubMed

    Finch, Caleb E; Austad, Steven N

    2012-10-01

    At later ages, humans have high risk of developing Alzheimer disease (AD) which may afflict up to 50% by 90 years. While prosimians and monkeys show more substantial changes, the great apes brains examined show mild neurodegenerative changes. Compared with rodents, primates develop and reproduce slowly and are long lived. The New World primates contain some of the shortest as well as some of the longest-lived monkey species, while the prosimians develop the most rapidly and are the shortest lived. Great apes have the largest brains, slowest development, and longest lives among the primates. All primates share some level of slowly progressive, age-related neurodegenerative changes. However, no species besides humans has yet shown regular drastic neuron loss or cognitive decline approaching clinical grade AD. Several primates accumulate extensive deposits of diffuse amyloid-beta protein (Aβ) but only a prosimian-the gray mouse lemur-regularly develops a tauopathy approaching the neurofibrillary tangles of AD. Compared with monkeys, nonhuman great apes display even milder brain-aging changes, a deeply puzzling observation. The genetic basis for these major species differences in brain aging remains obscure but does not involve the Aβ coding sequence which is identical in nonhuman primates and humans. While chimpanzees merit more study, we note the value of smaller, shorter-lived species such as marmosets and small lemurs for aging studies. A continuing concern for all aging studies employing primates is that relative to laboratory rodents, primate husbandry is in a relatively primitive state, and better husbandry to control infections and obesity is needed for brain aging research.

  6. Brain plasticity and motor practice in cognitive aging.

    PubMed

    Cai, Liuyang; Chan, John S Y; Yan, Jin H; Peng, Kaiping

    2014-01-01

    For more than two decades, there have been extensive studies of experience-based neural plasticity exploring effective applications of brain plasticity for cognitive and motor development. Research suggests that human brains continuously undergo structural reorganization and functional changes in response to stimulations or training. From a developmental point of view, the assumption of lifespan brain plasticity has been extended to older adults in terms of the benefits of cognitive training and physical therapy. To summarize recent developments, first, we introduce the concept of neural plasticity from a developmental perspective. Secondly, we note that motor learning often refers to deliberate practice and the resulting performance enhancement and adaptability. We discuss the close interplay between neural plasticity, motor learning and cognitive aging. Thirdly, we review research on motor skill acquisition in older adults with, and without, impairments relative to aging-related cognitive decline. Finally, to enhance future research and application, we highlight the implications of neural plasticity in skills learning and cognitive rehabilitation for the aging population.

  7. Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging

    PubMed Central

    Maimaiti, Shaniya; Anderson, Katie L.; DeMoll, Chris; Brewer, Lawrence D.; Rauh, Benjamin A.; Gant, John C.; Blalock, Eric M.; Porter, Nada M.

    2016-01-01

    Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer’s disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca2+-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP. PMID:25659889

  8. Effect of accelerated aging on the cross-link density of medical grade silicones.

    PubMed

    Mahomed, Aziza; Pormehr, Negin Bagheri

    2016-11-25

    Four specimens of Nagor silicone of different hardness (soft, medium and hard) were swollen, until they reached equilibrium (i.e. constant mass) in five liquids at 25°C, before and after accelerated aging. For the specimens swollen before accelerated aging, the greatest swelling was obtained in methyl cyclohexane, while for the specimens swollen after accelerated aging, the greatest swelling was obtained in cyclohexane. The cross-link density, υ, was also calculated from the swelling measurements for all the specimens, before and after accelerated aging, using the Flory-Rehner equation. The softer silicones, which swelled the most, had lower υ values than harder silicones. The amount of swelling (measured in terms of ϕ) and υ varied significantly (p<0.05) in some cases, between the different silicone hardness and between different liquids. Furthermore, the cross-link density, υ, significantly (p<0.05) increased after accelerated aging in most liquids.Note: ϕ is defined as the volume fraction of polymer in its equilibrium swollen state. A probability value of statistical significance of 0.05 or 5% was selected, hence if a p value of less than 0.05 was obtained, the null hypothesis was rejected (i.e. significant if p<0.05).

  9. A Healthy Middle-Aged Heart May Protect Your Brain Later

    MedlinePlus

    ... A Healthy Middle-Aged Heart May Protect Your Brain Later Dementia expert says take up heart-healthy ... 11, 2017 (HealthDay News) -- Healthy aging of the brain relies on the health of your heart and ...

  10. A 32-Channel Head Coil Array with Circularly Symmetric Geometry for Accelerated Human Brain Imaging

    PubMed Central

    Chu, Ying-Hua; Hsu, Yi-Cheng; Keil, Boris; Kuo, Wen-Jui; Lin, Fa-Hsuan

    2016-01-01

    The goal of this study is to optimize a 32-channel head coil array for accelerated 3T human brain proton MRI using either a Cartesian or a radial k-space trajectory. Coils had curved trapezoidal shapes and were arranged in a circular symmetry (CS) geometry. Coils were optimally overlapped to reduce mutual inductance. Low-noise pre-amplifiers were used to further decouple between coils. The SNR and noise amplification in accelerated imaging were compared to results from a head coil array with a soccer-ball (SB) geometry. The maximal SNR in the CS array was about 120% (1070 vs. 892) and 62% (303 vs. 488) of the SB array at the periphery and the center of the FOV on a transverse plane, respectively. In one-dimensional 4-fold acceleration, the CS array has higher averaged SNR than the SB array across the whole FOV. Compared to the SB array, the CS array has a smaller g-factor at head periphery in all accelerated acquisitions. Reconstructed images using a radial k-space trajectory show that the CS array has a smaller error than the SB array in 2- to 5-fold accelerations. PMID:26909652

  11. Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia.

    PubMed

    Zhang, Yiting; Hodgson, Nathaniel W; Trivedi, Malav S; Abdolmaleky, Hamid M; Fournier, Margot; Cuenod, Michel; Do, Kim Quang; Deth, Richard C

    2016-01-01

    Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders.

  12. Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia

    PubMed Central

    Zhang, Yiting; Hodgson, Nathaniel W.; Trivedi, Malav S.; Abdolmaleky, Hamid M.; Fournier, Margot; Cuenod, Michel; Do, Kim Quang; Deth, Richard C.

    2016-01-01

    Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders. PMID:26799654

  13. Influence of Patient Age on Angioarchitecture of Brain Arteriovenous Malformations

    PubMed Central

    Hetts, Steven W.; Cooke, Daniel L.; Nelson, Jeffrey; Gupta, Nalin; Fullerton, Heather; Amans, Matthew R.; Narvid, Jared A.; Moftakhar, Parham; McSwain, Hugh; Dowd, Christopher F.; Higashida, Randall T.; Halbach, Van V.; Lawton, Michael T.; Kim, Helen

    2014-01-01

    Background and Purpose To determine if clinical and angioarchitectural features of brain AVMs differ between children and adults. Materials and Methods A prospectively collected institutional database of all patients diagnosed with brain AVMs since 2001 was queried. Demographic, clinical, and angioarchitecture information was summarized and analyzed with univariable and multivariable models. Results Results often differed when age was treated as a continuous variable as opposed to dividing subjects into children (≤18 years; n=203) versus adults (>18 years; n=630). Children were more likely to present with AVM hemorrhage than adults (59% vs. 41%, p<0.001). Although AVMs with a larger nidus presented at younger ages (mean of 26.8 years for >6 cm compared to 37.1 years for <3 cm), this was not significantly different between children and adults (p=0.069). Exclusively deep venous drainage was more common in younger subjects both when age was treated continuously (p=0.04), or dichotomized (p<0.001). Venous ectasia was more common with increasing age (mean, 39.4 years with ectasia compared to 31.1 years without ectasia) and when adults were compared to children (52% vs. 35%, p<0.001). Patients with feeding artery aneurysms presented at later average age (44.1 years) than those without such aneurysms (31.6 years); this observation persisted when comparing children to adults (13% vs. 29%, p<0.001). Conclusion Although children with brain AVMs were more likely to come to clinical attention due to hemorrhage than adults, venous ectasia and feeding artery aneurysms were underrepresented in children, suggesting that these particular high risk features take time to develop. PMID:24627452

  14. [Morphological changes of neurons and neuroglial cells in the brain of senescence-accelerated prone 1 (SAMP1) mice].

    PubMed

    Khudoerkov, R M; Sal'kov, V N; Sal'nikova, O V; Sobolev, V B

    2014-01-01

    Computerized morphometry was used to examine the sizes of neuronal bodies and the compactness of arrangement of neurons and neuroglial cells in layers III and V of the sensorimotor cortex in senescence-accelerated prone 1 (SAMP1) mice (an experimental group) and senescence-accelerated-resistant strain 1 (SAMR1) ones (a control group). In the SAMP1 mice as compared to the SAMR1 ones, the neuronal body sizes were significantly unchanged; the compactness of their arrangement decreased by 17 and 20% in layers III and V, respectively; that of neuroglial cells significantly increased by 14% in layer III only. In the SAMP1 mice versus the SAMR1 ones, the glial index rose by 36% in layer III and by 24% in layer V. During simulation of physiological aging, the sizes of neuronal bodies were shown to be virtually unchanged in the cerebral cortex; the compactness of their arrangement (cell counts) moderately reduced and that of neuroglial cells increased, which caused a rise in the glioneuronal index that was indicative of the enhanced supporting function of neuroglial cells during the physiological aging of brain structures.

  15. Indestructible plastic: the neuroscience of the new aging brain

    PubMed Central

    Holman, Constance; de Villers-Sidani, Etienne

    2014-01-01

    In recent years, research on experience-dependent plasticity has provided valuable insight on adaptation to environmental input across the lifespan, and advances in understanding the minute cellular changes underlying the brain’s capacity for self-reorganization have opened exciting new possibilities for treating illness and injury. Ongoing work in this line of inquiry has also come to deeply influence another field: cognitive neuroscience of the normal aging. This complex process, once considered inevitable or beyond the reach of treatment, has been transformed into an arena of intense investigation and strategic intervention. However, important questions remain about this characterization of the aging brain, and the assumptions it makes about the social, cultural, and biological space occupied by cognition in the older individual and body. The following paper will provide a critical examination of the move from basic experiments on the neurophysiology of experience-dependent plasticity to the growing market for (and public conception of) cognitive aging as a medicalized space for intervention by neuroscience-backed technologies. Entangled with changing concepts of normality, pathology, and self-preservation, we will argue that this new understanding, led by personalized cognitive training strategies, is approaching a point where interdisciplinary research is crucial to provide a holistic and nuanced understanding of the aging process. This new outlook will allow us to move forward in a space where our knowledge, like our new conception of the brain, is never static. PMID:24782746

  16. CircRNA accumulation in the aging mouse brain

    PubMed Central

    Gruner, Hannah; Cortés-López, Mariela; Cooper, Daphne A.; Bauer, Matthew; Miura, Pedro

    2016-01-01

    Circular RNAs (circRNAs) are a newly appreciated class of RNAs expressed across diverse phyla. These enigmatic transcripts are most commonly generated by back-splicing events from exons of protein-coding genes. This results in highly stable RNAs due to the lack of free 5′ and 3′ ends. CircRNAs are enriched in neural tissues, suggesting that they might have neural functions. Here, we sought to determine whether circRNA accumulation occurs during aging in mice. Total RNA-seq profiling of young (1 month old) and aged (22 month old) cortex, hippocampus and heart samples was performed. This led to the confident detection of 6,791 distinct circRNAs across these samples, including 675 novel circRNAs. Analysis uncovered a strong bias for circRNA upregulation during aging in neural tissues. These age-accumulation trends were verified for individual circRNAs by RT-qPCR and Northern analysis. In contrast, comparison of aged versus young hearts failed to reveal a global trend for circRNA upregulation. Age-accumulation of circRNAs in brain tissues was found to be largely independent from linear RNA expression of host genes. These findings suggest that circRNAs might play biological roles relevant to the aging nervous system. PMID:27958329

  17. How age of acquisition influences brain architecture in bilinguals

    PubMed Central

    Wei, Miao; Joshi, Anand A.; Zhang, Mingxia; Mei, Leilei; Manis, Franklin R.; He, Qinghua; Beattie, Rachel L.; Xue, Gui; Shattuck, David W.; Leahy, Richard M.; Xue, Feng; Houston, Suzanne M.; Chen, Chuansheng; Dong, Qi; Lu, Zhong-Lin

    2016-01-01

    In the present study, we explored how Age of Acquisition (AoA) of L2 affected brain structures in bilingual individuals. Thirty-six native English speakers who were bilingual were scanned with high resolution MRI. After MRI signal intensity inhomogeneity correction, we applied both voxel-based morphometry (VBM) and surface-based morphometry (SBM) approaches to the data. VBM analysis was performed using FSL’s standard VBM processing pipeline. For the SBM analysis, we utilized a semi-automated sulci delineation procedure, registered the brains to an atlas, and extracted measures of twenty four pre-selected regions of interest. We addressed three questions: (1) Which areas are more susceptible to differences in AoA? (2) How do AoA, proficiency and current level of exposure work together in predicting structural differences in the brain? And (3) What is the direction of the effect of AoA on regional volumetric and surface measures? Both VBM and SBM results suggested that earlier second language exposure was associated with larger volumes in the right parietal cortex. Consistently, SBM showed that the cortical area of the right superior parietal lobule increased as AoA decreased. In contrast, in the right pars orbitalis of the inferior frontal gyrus, AoA, proficiency, and current level of exposure are equally important in accounting for the structural differences. We interpret our results in terms of current theory and research on the effects of L2 learning on brain structures and functions. PMID:27695193

  18. Age differences in the brain mechanisms of good taste.

    PubMed

    Rolls, Edmund T; Kellerhals, Michele B; Nichols, Thomas E

    2015-06-01

    There is strong evidence demonstrating age-related differences in the acceptability of foods and beverages. To examine the neural foundations underlying these age-related differences in the acceptability of different flavors and foods, we performed an fMRI study to investigate brain and hedonic responses to orange juice, orange soda, and vegetable juice in three different age groups: Young (22), Middle (40) and Elderly (60 years). Orange juice and orange soda were found to be liked by all age groups, while vegetable juice was disliked by the Young, but liked by the Elderly. In the insular primary taste cortex, the activations to these stimuli were similar in the 3 age groups, indicating that the differences in liking for these stimuli between the 3 groups were not represented in this first stage of cortical taste processing. In the agranular insula (anterior to the insular primary taste cortex) where flavor is represented, the activations to the stimuli were similar in the Elderly, but in the Young the activations were larger to the vegetable juice than to the orange drinks; and the activations here were correlated with the unpleasantness of the stimuli. In the anterior midcingulate cortex, investigated as a site where the activations were correlated with the unpleasantness of the stimuli, there was again a greater activation to the vegetable than to the orange stimuli in the Young but not in the Elderly. In the amygdala (and orbitofrontal cortex), investigated as sites where the activations were correlated with the pleasantness of the stimuli, there was a smaller activation to the vegetable than to the orange stimuli in the Young but not in the Elderly. The Middle group was intermediate with respect to the separation of their activations to the stimuli in the brain areas that represent the pleasantness or unpleasantness of flavors. Thus age differences in the activations to different flavors can in some brain areas be related to, and probably cause, the

  19. Reversal of glial and neurovascular markers of unhealthy brain aging by exercise in middle-aged female mice.

    PubMed

    Latimer, Caitlin S; Searcy, James L; Bridges, Michael T; Brewer, Lawrence D; Popović, Jelena; Blalock, Eric M; Landfield, Philip W; Thibault, Olivier; Porter, Nada M

    2011-01-01

    Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms, many which highlight its neuroprotective role via actions that enhance neurogenesis, neuronal morphology and/or neurotrophin release. However, the brain is also composed of glial and vascular elements, and comparatively less is known regarding the effects of exercise on these components in the aging brain. Here, we show that aerobic exercise at mid-age decreased markers of unhealthy brain aging including astrocyte hypertrophy, a hallmark of brain aging. Middle-aged female mice were assigned to a sedentary group or provided a running wheel for six weeks. Exercise decreased hippocampal astrocyte and myelin markers of aging but increased VEGF, a marker of angiogenesis. Brain vascular casts revealed exercise-induced structural modifications associated with improved endothelial function in the periphery. Our results suggest that age-related astrocyte hypertrophy/reactivity and myelin dysregulation are aggravated by a sedentary lifestyle and accompanying reductions in vascular function. However, these effects appear reversible with exercise initiated at mid-age. As this period of the lifespan coincides with the appearance of multiple markers of brain aging, including initial signs of cognitive decline, it may represent a window of opportunity for intervention as the brain appears to still possess significant vascular plasticity. These results may also have particular implications for aging females who are more susceptible than males to certain risk factors which contribute to vascular aging.

  20. Can Endocrine Disruptors Influence Neuroplasticity In The Aging Brain?

    PubMed Central

    Weiss, Bernard

    2007-01-01

    Only within the last two decades has the adult mammalian brain been recognized for its ability to generate new nerve cells and other neural structures and in essence to rewire itself. Although hippocampal structures have received the greatest scrutiny, other sites, including the cerebral cortex, also display this potential. Such processes remain active in the aging brain, although to a lesser degree. Two of the factors known to induce neurogenesis are environmental enrichment and physical activity. Gonadal hormones, however, also play crucial roles. Androgens and estrogens are both required for the preservation of cognitive function during aging and apparently help counteract the risk of Alzheimer’s disease. One overlooked threat to hormonal adequacy that requires close examination is the abundance of environmental endocrine-disrupting chemicals that interfere with gonadal function. They come in the form of estrogenic mimics, androgen mimics, anti-estrogens, anti-androgens, and in a variety of other guises. Because our brains are in continuous transition throughout the lifespan, responding both to environmental circumstances and to changing levels of gonadal steroids, endocrine-disrupting chemicals possess the potential to impair neurogenesis, and represent a hazard for the preservation of cognitive function during the later stages of the life cycle. PMID:17350099

  1. Accelerated Whole-Brain Multi-Parameter Mapping using Blind Compressed Sensing

    PubMed Central

    Bhave, Sampada; Lingala, Sajan Goud; Johnson, Casey P.; Magnotta, Vincent A.; Jacob, Mathews

    2015-01-01

    Purpose To introduce a blind compressed sensing (BCS) framework to accelerate multi-parameter MR mapping, and demonstrate its feasibility in high-resolution, whole-brain T1ρ and T2 mapping. Methods BCS models the evolution of magnetization at every pixel as a sparse linear combination of bases in a dictionary. Unlike compressed sensing (CS), the dictionary and the sparse coefficients are jointly estimated from under-sampled data. Large number of non-orthogonal bases in BCS accounts for more complex signals than low rank representations. The low degree of freedom of BCS, attributed to sparse coefficients, translates to fewer artifacts at high acceleration factors(R). Results From 2D retrospective under-sampling experiments, the mean square errors in T1ρ and T2 maps were observed to be within 0.1% up to R=10. BCS was observed to be more robust to patient-specific motion as compared to other CS schemes and resulted in minimal degradation of parameter maps in the presence of motion. Our results suggested that BCS can provide an acceleration factor of 8 in prospective 3D imaging with reasonable reconstructions. Conclusion BCS considerably reduces scan time for multi-parameter mapping of the whole brain with minimal artifacts, and is more robust to motion-induced signal changes compared to current CS and PCA based techniques. PMID:25850952

  2. Accelerated ageing and renal dysfunction links lower socioeconomic status and dietary phosphate intake

    PubMed Central

    McClelland, Ruth; Christensen, Kelly; Mohammed, Suhaib; McGuinness, Dagmara; Cooney, Josephine; Bakshi, Andisheh; Demou, Evangelia; MacDonald, Ewan; Caslake, Muriel; Stenvinkel, Peter; Shiels, Paul G.

    2016-01-01

    Background We have sought to explore the impact of dietary Pi intake on human age related health in the pSoBid cohort (n=666) to explain the disparity between health and deprivation status in this cohort. As hyperphosphataemia is a driver of accelerated ageing in rodent models of progeria we tested whether variation in Pi levels in man associate with measures of biological ageing and health. Results We observed significant relationships between serum Pi levels and markers of biological age (telomere length (p=0.040) and DNA methylation content (p=0.028), gender and chronological age (p=0.032). When analyses were adjusted for socio-economic status and nutritional factors, associations were observed between accelerated biological ageing (telomere length, genomic methylation content) and dietary derived Pi levels among the most deprived males, directly related to the frequency of red meat consumption. Conclusions Accelerated ageing is associated with high serum Pi levels and frequency of red meat consumption. Our data provide evidence for a mechanistic link between high intake of Pi and age-related morbidities tied to socio-economic status. PMID:27132985

  3. Fetal autonomic brain age scores, segmented heart rate variability analysis, and traditional short term variability

    PubMed Central

    Hoyer, Dirk; Kowalski, Eva-Maria; Schmidt, Alexander; Tetschke, Florian; Nowack, Samuel; Rudolph, Anja; Wallwitz, Ulrike; Kynass, Isabelle; Bode, Franziska; Tegtmeyer, Janine; Kumm, Kathrin; Moraru, Liviu; Götz, Theresa; Haueisen, Jens; Witte, Otto W.; Schleußner, Ekkehard; Schneider, Uwe

    2014-01-01

    Disturbances of fetal autonomic brain development can be evaluated from fetal heart rate patterns (HRP) reflecting the activity of the autonomic nervous system. Although HRP analysis from cardiotocographic (CTG) recordings is established for fetal surveillance, temporal resolution is low. Fetal magnetocardiography (MCG), however, provides stable continuous recordings at a higher temporal resolution combined with a more precise heart rate variability (HRV) analysis. A direct comparison of CTG and MCG based HRV analysis is pending. The aims of the present study are: (i) to compare the fetal maturation age predicting value of the MCG based fetal Autonomic Brain Age Score (fABAS) approach with that of CTG based Dawes-Redman methodology; and (ii) to elaborate fABAS methodology by segmentation according to fetal behavioral states and HRP. We investigated MCG recordings from 418 normal fetuses, aged between 21 and 40 weeks of gestation. In linear regression models we obtained an age predicting value of CTG compatible short term variability (STV) of R2 = 0.200 (coefficient of determination) in contrast to MCG/fABAS related multivariate models with R2 = 0.648 in 30 min recordings, R2 = 0.610 in active sleep segments of 10 min, and R2 = 0.626 in quiet sleep segments of 10 min. Additionally segmented analysis under particular exclusion of accelerations (AC) and decelerations (DC) in quiet sleep resulted in a novel multivariate model with R2 = 0.706. According to our results, fMCG based fABAS may provide a promising tool for the estimation of fetal autonomic brain age. Beside other traditional and novel HRV indices as possible indicators of developmental disturbances, the establishment of a fABAS score normogram may represent a specific reference. The present results are intended to contribute to further exploration and validation using independent data sets and multicenter research structures. PMID:25505399

  4. Coenzyme Q10 prevents accelerated cardiac aging in a rat model of poor maternal nutrition and accelerated postnatal growth.

    PubMed

    Tarry-Adkins, Jane L; Blackmore, Heather L; Martin-Gronert, Malgorzata S; Fernandez-Twinn, Denise S; McConnell, Josie M; Hargreaves, Iain P; Giussani, Dino A; Ozanne, Susan E

    2013-01-01

    Studies in human and animals have demonstrated that nutritionally induced low birth-weight followed by rapid postnatal growth increases the risk of metabolic syndrome and cardiovascular disease. Although the mechanisms underlying such nutritional programming are not clearly defined, increased oxidative-stress leading to accelerated cellular aging has been proposed to play an important role. Using an established rodent model of low birth-weight and catch-up growth, we show here that post-weaning dietary supplementation with coenzyme Q10, a key component of the electron transport chain and a potent antioxidant rescued many of the detrimental effects of nutritional programming on cardiac aging. This included a reduction in nitrosative and oxidative-stress, telomere shortening, DNA damage, cellular senescence and apoptosis. These findings demonstrate the potential for postnatal antioxidant intervention to reverse deleterious phenotypes of developmental programming and therefore provide insight into a potential translatable therapy to prevent cardiovascular disease in at risk humans.

  5. The role of the brain in female reproductive aging.

    PubMed

    Downs, Jodi L; Wise, Phyllis M

    2009-02-05

    In middle-aged women, follicular depletion is a critical factor mediating the menopausal transition; however, all levels of the hypothalamic-pituitary-gonadal (HPG) axis contribute to the age-related decline in reproductive function. To help elucidate the complex interactions between the ovary and brain during middle-age that lead to the onset of the menopause, we utilize animal models which share striking similarities in reproductive physiology. Our results show that during middle-age, prior to any overt irregularities in estrous cyclicity, the ability of 17beta-estradiol (E(2)) to modulate the cascade of neurochemical events required for preovulatory gonadotropin-releasing hormone (GnRH) release and a luteinizing hormone (LH) surge is diminished. Middle-aged female rats experience a delay in and an attenuation of LH release in response to E(2). Additionally, although we do not observe a decrease in GnRH neuron number until a very advanced age, E(2)-mediated GnRH neuronal activation declines during the earliest stages of age-related reproductive decline. Numerous hypothalamic neuropeptides and neurochemical stimulatory inputs (i.e., glutamate, norepinephrine (NE), and vasoactive intestinal peptide (VIP)) that drive the E(2)-mediated GnRH/LH surge appear to dampen with age or lack the precise temporal coordination required for a specific pattern of GnRH secretion, while inhibitory signals such as gamma-aminobutyric acid (GABA) and opioid peptides remain unchanged or elevated during the afternoon of proestrus. These changes, occurring at the level of the hypothalamus, lead to irregular estrous cycles and, ultimately, the cessation of reproductive function. Taken together, our studies indicate that the hypothalamus is an important contributor to age-related female reproductive decline.

  6. Docosahexaenoic Acid and the Aging Brain1–3

    PubMed Central

    Lukiw, Walter J.; Bazan, Nicolas G.

    2008-01-01

    The dietary essential PUFA docosahexaenoic acid [DHA; 22:6(n-3)] is a critical contributor to cell structure and function in the nervous system, and deficits in DHA abundance are associated with cognitive decline during aging and in neurodegenerative disease. Recent studies underscore the importance of DHA-derived neuroprotectin D1 (NPD1) in the homeostatic regulation of brain cell survival and repair involving neurotrophic, antiapoptotic and antiinflammatory signaling. Emerging evidence suggests that NPD1 synthesis is activated by growth factors and neurotrophins. Evolving research indicates that NPD1 has important determinant and regulatory interactions with the molecular-genetic mechanisms affecting β-amyloid precursor protein (βAPP) and amyloid beta (Aβ) peptide neurobiology. Deficits in DHA or its peroxidation appear to contribute to inflammatory signaling, apoptosis, and neuronal dysfunction in Alzheimer disease (AD), a common and progressive age-related neurological disorder unique to structures and processes of the human brain. This article briefly reviews our current understanding of the interactions of DHA and NPD1 on βAPP processing and Aβ peptide signaling and how this contributes to oxidative and pathogenic processes characteristic of aging and AD pathology. PMID:19022980

  7. Neural Plastic Effects of Cognitive Training on Aging Brain.

    PubMed

    Leung, Natalie T Y; Tam, Helena M K; Chu, Leung W; Kwok, Timothy C Y; Chan, Felix; Lam, Linda C W; Woo, Jean; Lee, Tatia M C

    2015-01-01

    Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group (n = 109) and the Active Control Group (n = 100). Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age.

  8. Seismic-fragility tests of new and accelerated-aged Class 1E battery cells

    SciTech Connect

    Bonzon, L.L.; Janis, W.J.; Black, D.A.; Paulsen, G.A.

    1987-01-01

    The seismic-fragility response of naturally-aged nuclear station safety-related batteries is of interest for two reasons: (1) to determine actual failure modes and thresholds and (2) to determine the validity of using the electrical capacity of individual cells as an indicator of the potential survivability of a battery given a seismic event. Prior reports in this series discussed the seismic-fragility tests and results for three specific naturally-aged cell types: 12-year old NCX-2250, 10-year old LCU-13, and 10-year old FHC-19. This report focuses on the complementary approach, namely, the seismic-fragility response of accelerated-aged batteries. Of particular interest is the degree to which such approaches accurately reproduce the actual failure modes and thresholds. In these tests the significant aging effects observed, in terms of seismic survivability, were: embrittlement of cell cases, positive bus material and positive plate grids; and excessive sulphation of positive plate active material causing hardening and expansion of positive plates. The IEEE Standard 535 accelerated aging method successfully reproduced seismically significant aging effects in new cells but accelerated grid embrittlement an estimated five years beyond the conditional age of other components.

  9. Towards Accelerated Aging Methodologies and Health Management of Power MOSFETs (Technical Brief)

    NASA Technical Reports Server (NTRS)

    Celaya, Jose R.; Patil, Nishad; Saha, Sankalita; Wysocki, Phil; Goebel, Kai

    2009-01-01

    Understanding aging mechanisms of electronic components is of extreme importance in the aerospace domain where they are part of numerous critical subsystems including avionics. In particular, power MOSFETs are of special interest as they are involved in high voltage switching circuits such as drivers for electrical motors. With increased use of electronics in aircraft control, it becomes more important to understand the degradation of these components in aircraft specific environments. In this paper, we present an accelerated aging methodology for power MOSFETs that subject the devices to indirect thermal overstress during high voltage switching. During this accelerated aging process, two major modes of failure were observed - latch-up and die attach degradation. In this paper we present the details of our aging methodology along with details of experiments and analysis of the results.

  10. Effect of age, behaviour and social environment on honey bee brain plasticity.

    PubMed

    Maleszka, Joanna; Barron, Andrew B; Helliwell, Paul G; Maleszka, Ryszard

    2009-08-01

    We examined the effects of behaviour, age and social environment on mushroom body volume in adult bees. The mushroom bodies are regions of the central brain important for sensory integration and learning. Their volume was influenced by behaviour throughout life: always larger in forager bees than age-matched nurse bees, even in old bees up to 93 days of age as adults. Mushroom body development was influenced by the social environment in the first 8 days of adult life, with different environments having markedly different effects on mushroom body size. Compared to hive-reared bees, isolation slowed mushroom body growth, but bees reared in isolation confined with a single dead bee showed a dramatic increase in mushroom body volume comparable to that seen in active foragers. Despite their precocious mushroom body development, these bees did not show improved performance in an olfactory learning test. Since simple environmental manipulations can both accelerate and delay mushroom body growth in young bees, and since mushroom body volume is sensitive to behaviour throughout life, the honey bee has great potential as a model for exploring the interactions between environment, behaviour and brain structure.

  11. Using autopsy brain tissue to study alcohol-related brain damage in the genomic age.

    PubMed

    Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

    2014-01-01

    The New South Wales Tissue Resource Centre at the University of Sydney, Australia, is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency, and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain damage (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular, it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539).

  12. Microglial cell dysregulation in brain aging and neurodegeneration.

    PubMed

    von Bernhardi, Rommy; Eugenín-von Bernhardi, Laura; Eugenín, Jaime

    2015-01-01

    Aging is the main risk factor for neurodegenerative diseases. In aging, microglia undergoes phenotypic changes compatible with their activation. Glial activation can lead to neuroinflammation, which is increasingly accepted as part of the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). We hypothesize that in aging, aberrant microglia activation leads to a deleterious environment and neurodegeneration. In aged mice, microglia exhibit an increased expression of cytokines and an exacerbated inflammatory response to pathological changes. Whereas LPS increases nitric oxide (NO) secretion in microglia from young mice, induction of reactive oxygen species (ROS) predominates in older mice. Furthermore, there is accumulation of DNA oxidative damage in mitochondria of microglia during aging, and also an increased intracellular ROS production. Increased ROS activates the redox-sensitive nuclear factor kappa B, which promotes more neuroinflammation, and can be translated in functional deficits, such as cognitive impairment. Mitochondria-derived ROS and cathepsin B, are also necessary for the microglial cell production of interleukin-1β, a key inflammatory cytokine. Interestingly, whereas the regulatory cytokine TGFβ1 is also increased in the aged brain, neuroinflammation persists. Assessing this apparent contradiction, we have reported that TGFβ1 induction and activation of Smad3 signaling after inflammatory stimulation are reduced in adult mice. Other protective functions, such as phagocytosis, although observed in aged animals, become not inducible by inflammatory stimuli and TGFβ1. Here, we discuss data suggesting that mitochondrial and endolysosomal dysfunction could at least partially mediate age-associated microglial cell changes, and, together with the impairment of the TGFβ1-Smad3 pathway, could result in the reduction of protective activation and the facilitation of cytotoxic activation of microglia, resulting in the promotion of

  13. Microglial cell dysregulation in brain aging and neurodegeneration

    PubMed Central

    von Bernhardi, Rommy; Eugenín-von Bernhardi, Laura; Eugenín, Jaime

    2015-01-01

    Aging is the main risk factor for neurodegenerative diseases. In aging, microglia undergoes phenotypic changes compatible with their activation. Glial activation can lead to neuroinflammation, which is increasingly accepted as part of the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD). We hypothesize that in aging, aberrant microglia activation leads to a deleterious environment and neurodegeneration. In aged mice, microglia exhibit an increased expression of cytokines and an exacerbated inflammatory response to pathological changes. Whereas LPS increases nitric oxide (NO) secretion in microglia from young mice, induction of reactive oxygen species (ROS) predominates in older mice. Furthermore, there is accumulation of DNA oxidative damage in mitochondria of microglia during aging, and also an increased intracellular ROS production. Increased ROS activates the redox-sensitive nuclear factor kappa B, which promotes more neuroinflammation, and can be translated in functional deficits, such as cognitive impairment. Mitochondria-derived ROS and cathepsin B, are also necessary for the microglial cell production of interleukin-1β, a key inflammatory cytokine. Interestingly, whereas the regulatory cytokine TGFβ1 is also increased in the aged brain, neuroinflammation persists. Assessing this apparent contradiction, we have reported that TGFβ1 induction and activation of Smad3 signaling after inflammatory stimulation are reduced in adult mice. Other protective functions, such as phagocytosis, although observed in aged animals, become not inducible by inflammatory stimuli and TGFβ1. Here, we discuss data suggesting that mitochondrial and endolysosomal dysfunction could at least partially mediate age-associated microglial cell changes, and, together with the impairment of the TGFβ1-Smad3 pathway, could result in the reduction of protective activation and the facilitation of cytotoxic activation of microglia, resulting in the promotion of

  14. Aging elevates metabolic gene expression in brain cholinergic neurons.

    PubMed

    Baskerville, Karen A; Kent, Caroline; Personett, David; Lai, Weil R; Park, Peter J; Coleman, Paul; McKinney, Michael

    2008-12-01

    The basal forebrain (BF) cholinergic system is selectively vulnerable in human brain diseases, while the cholinergic groups in the upper pons of the brainstem (BS) resist neurodegeneration. Cholinergic neurons (200 per region per animal) were laser-microdissected from five young (8 months) and five aged (24 months) F344 rats from the BF and the BS pontine lateral dorsal tegmental/pedunculopontine nuclei (LDTN/PPN) and their expression profiles were obtained. The bioinformatics program SigPathway was used to identify gene groups and pathways that were selectively affected by aging. In the BF cholinergic system, aging most significantly altered genes involved with a variety of metabolic functions. In contrast, BS cholinergic neuronal age effects included gene groupings related to neuronal plasticity and a broad range of normal cellular functions. Transcription factor GA-binding protein alpha (GABPalpha), which controls expression of nuclear genes encoding mitochondrial proteins, was more strongly upregulated in the BF cholinergic neurons (+107%) than in the BS cholinergic population (+40%). The results suggest that aging elicits elevates metabolic activity in cholinergic populations and that this occurs to a much greater degree in the BF group than in the BS group.

  15. Towards Prognostics of Power MOSFETs: Accelerated Aging and Precursors of Failure

    DTIC Science & Technology

    2010-10-01

    Annual Conference of the Prognostics and Health Management Society, 2010 Towards Prognostics of Power MOSFETs : Accelerated Aging and Precursors of...research results dealing with power MOSFETs (metal oxide semiconductor field effect tran- sistor) within the prognostics and health management of...electronics. Gate controlled power transistors like power MOSFETs (metal oxide semiconductor field effect tran- sistor) are power semiconductor

  16. Accelerated aging and discharge of lithium/thionyl-chloride D cells

    NASA Astrophysics Data System (ADS)

    Cieslak, W. R.

    Lithium/Thionyl-Chloride spiral wound 'D' cells from a variety of suppliers have been evaluated. Abuse testing has been used to verify safety of the cells, and accelerated aging has been used to estimate their performance for long life projects.

  17. Exposure to light at night accelerates aging and spontaneous uterine carcinogenesis in female 129/Sv mice

    PubMed Central

    Popovich, Irina G.; Zabezhinski, Mark A.; Panchenko, Andrei V.; Piskunova, Tatiana S.; Semenchenko, Anna V.; Tyndyk, Maragriata L.; Yurova, Maria N.; Anisimov, Vladimir N.

    2013-01-01

    The effect of the constant illumination on the development of spontaneous tumors in female 129/Sv mice was investigated. Forty-six female 129/Sv mice starting from the age of 2 mo were kept under standard light/dark regimen [12 h light (70 lx):12hr dark; LD, control group], and 46 of 129/Sv mice were kept under constant illumination (24 h a day, 2,500 lx, LL) from the age of 5 mo until to natural death. The exposure to the LL regimen significantly accelerated body weight gain, increased body temperature as well as acceleration of age-related disturbances in estrous function, followed by significant acceleration of the development of the spontaneous uterine tumors in female 129/Sv mice. Total tumor incidence as well as a total number of total or malignant tumors was similar in LL and LD group (p > 0.05). The mice from the LL groups survived less than those from the LD group (χ2 = 8.5; p = 0.00351, log-rank test). According to the estimated parameters of the Cox’s regression model, constant light regimen increased the relative risk of death in female mice compared with the control (LD) group (p = 0.0041). The data demonstrate in the first time that the exposure to constant illumination was followed by the acceleration of aging and spontaneous uterine tumorigenesis in female 129/Sv mice. PMID:23656779

  18. Effects of accelerated aging and p-coumaric on crimson clover (Trifolium incarnatium L.) seed germination.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several phenolic acids, including p-coumaric acid, have been described as allelochemicals that may inhibit seed germination or seedling growth. Whether these effects are exacerbated in forage species by environmental stressors is unknown. Accelerated seed aging (high temperature (41 C) and high hum...

  19. Metabolic acceleration and the evolution of human brain size and life history.

    PubMed

    Pontzer, Herman; Brown, Mary H; Raichlen, David A; Dunsworth, Holly; Hare, Brian; Walker, Kara; Luke, Amy; Dugas, Lara R; Durazo-Arvizu, Ramon; Schoeller, Dale; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Thompson, Melissa Emery; Shumaker, Robert W; Ross, Stephen R

    2016-05-19

    Humans are distinguished from the other living apes in having larger brains and an unusual life history that combines high reproductive output with slow childhood growth and exceptional longevity. This suite of derived traits suggests major changes in energy expenditure and allocation in the human lineage, but direct measures of human and ape metabolism are needed to compare evolved energy strategies among hominoids. Here we used doubly labelled water measurements of total energy expenditure (TEE; kcal day(-1)) in humans, chimpanzees, bonobos, gorillas and orangutans to test the hypothesis that the human lineage has experienced an acceleration in metabolic rate, providing energy for larger brains and faster reproduction without sacrificing maintenance and longevity. In multivariate regressions including body size and physical activity, human TEE exceeded that of chimpanzees and bonobos, gorillas and orangutans by approximately 400, 635 and 820 kcal day(-1), respectively, readily accommodating the cost of humans' greater brain size and reproductive output. Much of the increase in TEE is attributable to humans' greater basal metabolic rate (kcal day(-1)), indicating increased organ metabolic activity. Humans also had the greatest body fat percentage. An increased metabolic rate, along with changes in energy allocation, was crucial in the evolution of human brain size and life history.

  20. Metabolic acceleration and the evolution of human brain size and life history

    PubMed Central

    Pontzer, Herman; Brown, Mary H.; Raichlen, David A.; Dunsworth, Holly; Hare, Brian; Walker, Kara; Luke, Amy; Dugas, Lara R.; Durazo-Arvizu, Ramon; Schoeller, Dale; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E.; Lambert, Estelle V.; Thompson, Melissa Emery; Shumaker, Robert W.; Ross, Stephen R.

    2016-01-01

    Humans are distinguished from the other living apes in having larger brains and an unusual life history that combines high reproductive output with slow childhood growth and exceptional longevity1. This suite of derived traits suggests major changes in energy expenditure and allocation in the human lineage, but direct measures of human and ape metabolism are needed to compare evolved energy strategies among hominoids. Here we used doubly labelled water measurements of total energy expenditure (TEE; kcal day−1) in humans, chimpanzees, bonobos, gorillas and orangutans to test the hypothesis that the human lineage has experienced an acceleration in metabolic rate, providing energy for larger brains and faster reproduction without sacrificing maintenance and longevity. In multivariate regressions including body size and physical activity, human TEE exceeded that of chimpanzees and bonobos, gorillas and orangutans by approximately 400, 635 and 820 kcal day−1, respectively, readily accommodating the cost of humans' greater brain size and reproductive output. Much of the increase in TEE is attributable to humans' greater basal metabolic rate (kcal day−1), indicating increased organ metabolic activity. Humans also had the greatest body fat percentage. An increased metabolic rate, along with changes in energy allocation, was crucial in the evolution of human brain size and life history. PMID:27144364

  1. Accelerator-based epithermal neutron sources for boron neutron capture therapy of brain tumors.

    PubMed

    Blue, Thomas E; Yanch, Jacquelyn C

    2003-01-01

    This paper reviews the development of low-energy light ion accelerator-based neutron sources (ABNSs) for the treatment of brain tumors through an intact scalp and skull using boron neutron capture therapy (BNCT). A major advantage of an ABNS for BNCT over reactor-based neutron sources is the potential for siting within a hospital. Consequently, light-ion accelerators that are injectors to larger machines in high-energy physics facilities are not considered. An ABNS for BNCT is composed of: (1) the accelerator hardware for producing a high current charged particle beam, (2) an appropriate neutron-producing target and target heat removal system (HRS), and (3) a moderator/reflector assembly to render the flux energy spectrum of neutrons produced in the target suitable for patient irradiation. As a consequence of the efforts of researchers throughout the world, progress has been made on the design, manufacture, and testing of these three major components. Although an ABNS facility has not yet been built that has optimally assembled these three components, the feasibility of clinically useful ABNSs has been clearly established. Both electrostatic and radio frequency linear accelerators of reasonable cost (approximately 1.5 M dollars) appear to be capable of producing charged particle beams, with combinations of accelerated particle energy (a few MeV) and beam currents (approximately 10 mA) that are suitable for a hospital-based ABNS for BNCT. The specific accelerator performance requirements depend upon the charged particle reaction by which neutrons are produced in the target and the clinical requirements for neutron field quality and intensity. The accelerator performance requirements are more demanding for beryllium than for lithium as a target. However, beryllium targets are more easily cooled. The accelerator performance requirements are also more demanding for greater neutron field quality and intensity. Target HRSs that are based on submerged-jet impingement and

  2. Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function

    PubMed Central

    Issa, Abdul-Raouf; Seugnet, Laurent; Klarsfeld, André

    2017-01-01

    Circadian clocks control many self-sustained rhythms in physiology and behavior with approximately 24-hour periodicity. In many organisms, oxidative stress and aging negatively impact the circadian system and sleep. Conversely, loss of the clock decreases resistance to oxidative stress, and may reduce lifespan and speed up brain aging and neurodegeneration. Here we examined the effects of clock disruptions on locomotor aging and longevity in Drosophila. We found that lifespan was similarly reduced in three arrhythmic mutants (ClkAR, cyc0 and tim0) and in wild-type flies under constant light, which stops the clock. In contrast, ClkAR mutants showed significantly faster age-related locomotor deficits (as monitored by startle-induced climbing) than cyc0 and tim0, or than control flies under constant light. Reactive oxygen species accumulated more with age in ClkAR mutant brains, but this did not appear to contribute to the accelerated locomotor decline of the mutant. Clk, but not Cyc, inactivation by RNA interference in the pigment-dispersing factor (PDF)-expressing central pacemaker neurons led to similar loss of climbing performance as ClkAR. Conversely, restoring Clk function in these cells was sufficient to rescue the ClkAR locomotor phenotype, independently of behavioral rhythmicity. Accelerated locomotor decline of the ClkAR mutant required expression of the PDF receptor and correlated to an apparent loss of dopaminergic neurons in the posterior protocerebral lateral 1 (PPL1) clusters. This neuronal loss was rescued when the ClkAR mutation was placed in an apoptosis-deficient background. Impairing dopamine synthesis in a single pair of PPL1 neurons that innervate the mushroom bodies accelerated locomotor decline in otherwise wild-type flies. Our results therefore reveal a novel circadian-independent requirement for Clk in brain circadian neurons to maintain a subset of dopaminergic cells and avoid premature locomotor aging in Drosophila. PMID:28072817

  3. Age Sensitivity of Behavioral Tests and Brain Substrates of Normal Aging in Mice

    PubMed Central

    Kennard, John A.; Woodruff-Pak, Diana S.

    2011-01-01

    Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze, and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memory in rodents, which generalize in many cases to age-related changes in learning and memory in all mammals, including humans. Behavioral assessments are a valuable means to measure functional outcomes of neuroscientific studies of aging. Highlighted in this review are the attributes and limitations of these measures in mice in the context of age sensitivity and processes of brain aging. Attributes of these tests include reliability and validity as assessments of learning and memory, well-defined neural substrates, and sensitivity to neural and pharmacological manipulations and disruptions. These tests engage the hippocampus and/or the cerebellum, two structures centrally involved in learning and memory that undergo functional and anatomical changes in normal aging. A test that is less well represented in studies of normal aging, the context pre-exposure facilitation effect (CPFE) in fear conditioning, is described as a method to increase sensitivity of contextual fear conditioning to changes in the hippocampus. Recommendations for increasing the age sensitivity of all measures of normal aging in mice are included, as well as a discussion of the potential of the under-studied CPFE to advance understanding of subtle hippocampus-mediated phenomena. PMID:21647305

  4. Rationale for practical medical device accelerated aging programs in AAMI TIR 17

    NASA Astrophysics Data System (ADS)

    Lambert, Byron J.; Tang, Fuh-Wei

    2000-03-01

    A Technical Information Report, TIR 17, entitled, "Radiation Sterilization Material Qualification" has been published by the Association for the Advancement of Medical Instrumentation (AAMI) to provide guidance in order to increase the quality and reduce the cost and amount of time required for performing medical device material qualifications. It contains four sections that cover the fundamentals of material selection, processing, testing and accelerated aging programs. The last of these sections, entitled "Accelerating Aging Programs," provides step-by-step guidance for simple, empirical accelerated programs of use to the medical device industry. The methods are based on van't Hoff's observation that the rate of chemical reactions increases by a factor of two for every 10°C increase in temperature, the Q10=2 rule. With critical patient safety concerns in the medical device industry, it is appropriate for both device manufacturers and regulators to ask if simple, empirical methods such as those outlined in TIR 17 are reasonable and responsible. One reason for confidence in the methods is their success when used in aging environments that are much more severe than those commonly used in the medical device industry. Another reason for confidence in the methods is found from the observation that the working equations of the method can be derived from theory. This paper provides an overview of the thermal accelerated aging theory that forms the basis for the working equations of the accelerated aging programs of TIR 17. Assumptions used are examined and found reasonable; the theoretical foundation is established. While this foundation provides added confidence for the application of the methods of TIR 17 to the medical device industry, it is emphasized that application of the methods within appropriate boundaries is critical. Theoretical boundaries are explained and demonstrated by means of Arrhenius plots, and practical boundaries discussed.

  5. Role of walnuts in maintaining brain health with age.

    PubMed

    Poulose, Shibu M; Miller, Marshall G; Shukitt-Hale, Barbara

    2014-04-01

    Because of the combination of population growth and population aging, increases in the incidence of chronic neurodegenerative disorders have become a societal concern, both in terms of decreased quality of life and increased financial burden. Clinical manifestation of many of these disorders takes years, with the initiation of mild cognitive symptoms leading to behavioral problems, dementia and loss of motor functions, the need for assisted living, and eventual death. Lifestyle factors greatly affect the progression of cognitive decline, with high-risk behaviors including unhealthy diet, lack of exercise, smoking, and exposure to environmental toxins leading to enhanced oxidative stress and inflammation. Although there exists an urgent need to develop effective treatments for age-related cognitive decline and neurodegenerative disease, prevention strategies have been underdeveloped. Primary prevention in many of these neurodegenerative diseases could be achieved earlier in life by consuming a healthy diet, rich in antioxidant and anti-inflammatory phytochemicals, which offers one of the most effective and least expensive ways to address the crisis. English walnuts (Juglans regia L.) are rich in numerous phytochemicals, including high amounts of polyunsaturated fatty acids, and offer potential benefits to brain health. Polyphenolic compounds found in walnuts not only reduce the oxidant and inflammatory load on brain cells but also improve interneuronal signaling, increase neurogenesis, and enhance sequestration of insoluble toxic protein aggregates. Evidence for the beneficial effects of consuming a walnut-rich diet is reviewed in this article.

  6. Intelligence and brain size in 100 postmortem brains: sex, lateralization and age factors.

    PubMed

    Witelson, S F; Beresh, H; Kigar, D L

    2006-02-01

    The neural basis of variation in human intelligence is not well delineated. Numerous studies relating measures of brain size such as brain weight, head circumference, CT or MRI brain volume to different intelligence test measures, with variously defined samples of subjects have yielded inconsistent findings with correlations from approximately 0 to 0.6, with most correlations approximately 0.3 or 0.4. The study of intelligence in relation to postmortem cerebral volume is not available to date. We report the results of such a study on 100 cases (58 women and 42 men) having prospectively obtained Full Scale Wechsler Adult Intelligence Scale scores. Ability correlated with cerebral volume, but the relationship depended on the realm of intelligence studied, as well as the sex and hemispheric functional lateralization of the subject. General verbal ability was positively correlated with cerebral volume and each hemisphere's volume in women and in right-handed men accounting for 36% of the variation in verbal intelligence. There was no evidence of such a relationship in non-right-handed men, indicating that at least for verbal intelligence, functional asymmetry may be a relevant factor in structure-function relationships in men, but not in women. In women, general visuospatial ability was also positively correlated with cerebral volume, but less strongly, accounting for approximately 10% of the variance. In men, there was a non-significant trend of a negative correlation between visuospatial ability and cerebral volume, suggesting that the neural substrate of visuospatial ability may differ between the sexes. Analyses of additional research subjects used as test cases provided support for our regression models. In men, visuospatial ability and cerebral volume were strongly linked via the factor of chronological age, suggesting that the well-documented decline in visuospatial intelligence with age is related, at least in right-handed men, to the decrease in cerebral

  7. Rapid evaluation of the durability of cortical neural implants using accelerated aging with reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Takmakov, Pavel; Ruda, Kiersten; Phillips, K. Scott; Isayeva, Irada S.; Krauthamer, Victor; Welle, Cristin G.

    2015-04-01

    Objective. A challenge for implementing high bandwidth cortical brain-machine interface devices in patients is the limited functional lifespan of implanted recording electrodes. Development of implant technology currently requires extensive non-clinical testing to demonstrate device performance. However, testing the durability of the implants in vivo is time-consuming and expensive. Validated in vitro methodologies may reduce the need for extensive testing in animal models. Approach. Here we describe an in vitro platform for rapid evaluation of implant stability. We designed a reactive accelerated aging (RAA) protocol that employs elevated temperature and reactive oxygen species (ROS) to create a harsh aging environment. Commercially available microelectrode arrays (MEAs) were placed in a solution of hydrogen peroxide at 87 °C for a period of 7 days. We monitored changes to the implants with scanning electron microscopy and broad spectrum electrochemical impedance spectroscopy (1 Hz-1 MHz) and correlated the physical changes with impedance data to identify markers associated with implant failure. Main results. RAA produced a diverse range of effects on the structural integrity and electrochemical properties of electrodes. Temperature and ROS appeared to have different effects on structural elements, with increased temperature causing insulation loss from the electrode microwires, and ROS concentration correlating with tungsten metal dissolution. All array types experienced impedance declines, consistent with published literature showing chronic (>30 days) declines in array impedance in vivo. Impedance change was greatest at frequencies <10 Hz, and smallest at frequencies 1 kHz and above. Though electrode performance is traditionally characterized by impedance at 1 kHz, our results indicate that an impedance change at 1 kHz is not a reliable predictive marker of implant degradation or failure. Significance. ROS, which are known to be present in vivo, can create

  8. GeNN: a code generation framework for accelerated brain simulations

    NASA Astrophysics Data System (ADS)

    Yavuz, Esin; Turner, James; Nowotny, Thomas

    2016-01-01

    Large-scale numerical simulations of detailed brain circuit models are important for identifying hypotheses on brain functions and testing their consistency and plausibility. An ongoing challenge for simulating realistic models is, however, computational speed. In this paper, we present the GeNN (GPU-enhanced Neuronal Networks) framework, which aims to facilitate the use of graphics accelerators for computational models of large-scale neuronal networks to address this challenge. GeNN is an open source library that generates code to accelerate the execution of network simulations on NVIDIA GPUs, through a flexible and extensible interface, which does not require in-depth technical knowledge from the users. We present performance benchmarks showing that 200-fold speedup compared to a single core of a CPU can be achieved for a network of one million conductance based Hodgkin-Huxley neurons but that for other models the speedup can differ. GeNN is available for Linux, Mac OS X and Windows platforms. The source code, user manual, tutorials, Wiki, in-depth example projects and all other related information can be found on the project website http://genn-team.github.io/genn/.

  9. Accelerated recovery from acute brain injuries: clinical efficacy of neurotrophic treatment in stroke and traumatic brain injuries.

    PubMed

    Bornstein, N; Poon, W S

    2012-04-01

    Stroke is one of the most devastating vascular diseases in the world as it is responsible for almost five million deaths per year. Almost 90% of all strokes are ischemic and mainly due to atherosclerosis, cardiac embolism and small-vessel disease. Intracerebral or subarachnoid hemorrhage can lead to hemorrhagic stroke, which usually has the poorest prognosis. Cerebrolysin is a peptide preparation which mimics the action of a neurotrophic factor, protecting stroke-injured neurons and promoting neuroplasticity and neurogenesis. Cerebrolysin has been widely studied as a therapeutic tool for both ischemic and hemorrhagic stroke, as well as traumatic brain injury. In ischemic stroke, Cerebrolysin given as an adjuvant therapy to antiplatelet and rheologically active medication resulted in accelerated improvement in global, neurological and motor functions, cognitive performance and activities of daily living. Cerebrolysin was also safe and well tolerated when administered in patients suffering from hemorrhagic stroke. Traumatic brain injury leads to transient or chronic impairments in physical, cognitive, emotional and behavioral functions. This is associated with deficits in the recognition of basic emotions, the capacity to interpret the mental states of others, and executive functioning. Pilot clinical studies with adjuvant Cerebrolysin in the acute and postacute phases of the injury have shown faster recovery, which translates into an earlier onset of rehabilitation and shortened hospitalization time.

  10. Compatibility and accelerated aging study for Li(Si)/FeS/sub 2 thermally activated batteries

    NASA Astrophysics Data System (ADS)

    Mead, J. W.; Searcy, J. Q.; Neiswander, P. N.; Poole, R. L.

    1983-12-01

    Thermally activated batteries using the lithium (silicon) iron disulfide (Li(Si)/FeS2) electrochemical system are used in weapons having a required storage life of 25 years and high reliability. A review of known data revealed no information on the compatibility of Li(Si)/FeS2 with the organic materials used in the system. The compatibility question is studied. Accelerated-aging data on pairs of materials were produced. In addition, a group of production batteries was aged and tested. Three aging temperatures were used during the one-year study. Gas analyses, electrical tests and mechanical tests were compared for control and aged samples. Two results, the depletion of oxygen and an increase in hydrogen in the compatibility and accelerated-aging samples, stimulated additional studies. No unexpected or significant changes were observed in the electrical or mechanical properties of the organic materials. Calorific output and chloride ion content of heat pellets indicated no degradation with aging. Ignition sensitivity and burn rate measurements suggested no heat pellet degradation. Oxygen content in aged lithium (silicon) anodes remained within acceptable limits. Single-cell tests and battery test results showed no degradation with aging.

  11. Manganese-mediated acceleration of age-related hearing loss in mice

    PubMed Central

    Ohgami, Nobutaka; Yajima, Ichiro; Iida, Machiko; Li, Xiang; Oshino, Reina; Kumasaka, Mayuko Y.; Kato, Masashi

    2016-01-01

    Despite the fact that manganese (Mn) is known to be a neurotoxic element relevant to age-related disorders, the risk of oral exposure to Mn for age-related hearing loss remains unclear. In this study, we orally exposed wild-type young adult mice to Mn (Mn-exposed WT-mice) at 1.65 and 16.50 mg/L for 4 weeks. Mn-exposed WT-mice showed acceleration of age-related hearing loss. Mn-exposed WT-mice had neurodegeneration of spiral ganglion neurons (SGNs) with increased number of lipofuscin granules. Mn-exposed WT-mice also had increased hypoxia-inducible factor-1 alpha (Hif-1α) protein with less hydroxylation at proline 564 and decreased c-Ret protein in SGNs. Mn-mediated acceleration of age-related hearing loss involving neurodegeneration of SGNs was rescued in RET-transgenic mice carrying constitutively activated RET. Thus, oral exposure to Mn accelerates age-related hearing loss in mice with Ret-mediated neurodegeneration of SGNs. PMID:27824154

  12. The role of oxidative and nitrosative stress in accelerated aging and major depressive disorder.

    PubMed

    Maurya, Pawan Kumar; Noto, Cristiano; Rizzo, Lucas B; Rios, Adiel C; Nunes, Sandra O V; Barbosa, Décio Sabbatini; Sethi, Sumit; Zeni, Maiara; Mansur, Rodrigo B; Maes, Michael; Brietzke, Elisa

    2016-02-04

    Major depressive disorder (MDD) affects millions of individuals and is highly comorbid with many age associated diseases such as diabetes mellitus, immune-inflammatory dysregulation and cardiovascular diseases. Oxidative/nitrosative stress plays a fundamental role in aging, as well as in the pathogenesis of neurodegenerative/neuropsychiatric disorders including MDD. In this review, we critically review the evidence for an involvement of oxidative/nitrosative stress in acceleration of aging process in MDD. There are evidence of the association between MDD and changes in molecular mechanisms involved in aging. There is a significant association between telomere length, enzymatic antioxidant activities (SOD, CAT, GPx), glutathione (GSH), lipid peroxidation (MDA), nuclear factor κB, inflammatory cytokines with MDD. Major depression also is characterized by significantly lower concentration of antioxidants (zinc, coenzyme Q10, PON1). Since, aging and MDD share a common biological base in their pathophysiology, the potential therapeutic use of antioxidants and anti-aging molecules in MDD could be promising.

  13. Compatibility and accelerated aging study for Li(Si)/FeS2 thermally activated batteries

    NASA Astrophysics Data System (ADS)

    Mead, J. W.; Searcy, J. Q.; Neiswander, P. A.; Poole, R. L.

    Thermally activated batteries using Li(Si)/FeS2 for use in systems which require a storage life of 25 years and high reliability are examined. All of the materials in the system, both organic and inorganic are incorporated except the heat paper and electric match are studied. No compatibility or aging problems are indicated. The following results are reported: oxygen vanishes from the overgas in containers that were accelerated aged; hydrogen increases sharply in the overgas initially but generally decreases as aging progresses. No unexpected or significant changes were observed in the volume resistivity, glass transition temperature, or shear modulus or organic materials.

  14. Acceleration factors for oxidative aging of polymeric materials by oxygen detection.

    SciTech Connect

    Assink, Roger Alan; Celina, Mathias Christopher; Skutnik, Julie Michelle

    2005-01-01

    Three methods that were used to measure the chemical changes associated with oxidative degradation of polymeric materials are presented. The first method is based on the nuclear activation of {sup 18}O in an elastomer that was thermally aged in an {sup 18}O{sub 2} atmosphere. Second, the alcohol groups in a thermally aged elastomer were derivatized with trifluoroacetic anhydride and their concentration measured via {sup 19}F NMR spectroscopy. Finally, a respirometer was used to directly measure the oxidative rates of a polyurethane foam as a function of aging temperature. The measurement of the oxidation rates enabled acceleration factors for oxidative degradation of these materials to be calculated.

  15. Telomere length in subjects with schizophrenia, their unaffected siblings and healthy controls: Evidence of accelerated aging.

    PubMed

    Czepielewski, Leticia Sanguinetti; Massuda, Raffael; Panizzutti, Bruna; da Rosa, Eduarda Dias; de Lucena, David; Macêdo, Danielle; Grun, Lucas Kich; Barbé-Tuana, Florencia María; Gama, Clarissa Severino

    2016-07-01

    Schizophrenia (SZ) is associated with broad burden. The clinical manifestations of SZ are related to pathophysiological alterations similar to what is seen in normal aging. Our aim was to evaluate the differences in telomere length (TL), a biomarker of cellular aging, in subjects with SZ (n=36), unaffected siblings (SB, n=36) and healthy controls (HC, n=47). SZ had shorter TL compared to HC, but no difference was found in SB comparing to SZ. These findings indicate that a pathological accelerated aging profile could be present in the course of SZ and further studies are needed to confirm TL as potential endophenotype, especially in at risk populations.

  16. Brain network changes and memory decline in aging.

    PubMed

    Beason-Held, Lori L; Hohman, Timothy J; Venkatraman, Vijay; An, Yang; Resnick, Susan M

    2016-06-18

    One theory of age-related cognitive decline proposes that changes within the default mode network (DMN) of the brain impact the ability to successfully perform cognitive operations. To investigate this theory, we examined functional covariance within brain networks using regional cerebral blood flow data, measured by (15)O-water PET, from 99 participants (mean baseline age 68.6 ± 7.5) in the Baltimore Longitudinal Study of Aging collected over a 7.4 year period. The sample was divided in tertiles based on longitudinal performance on a verbal recognition memory task administered during scanning, and functional covariance was compared between the upper (improvers) and lower (decliners) tertile groups. The DMN and verbal memory networks (VMN) were then examined during the verbal memory scan condition. For each network, group differences in node-to-network coherence and individual node-to-node covariance relationships were assessed at baseline and in change over time. Compared with improvers, decliners showed differences in node-to-network coherence and in node-to-node relationships in the DMN but not the VMN during verbal memory. These DMN differences reflected greater covariance with better task performance at baseline and both increasing and declining covariance with declining task performance over time for decliners. When examined during the resting state alone, the direction of change in DMN covariance was similar to that seen during task performance, but node-to-node relationships differed from those observed during the task condition. These results suggest that disengagement of DMN components during task performance is not essential for successful cognitive performance as previously proposed. Instead, a proper balance in network processes may be needed to support optimal task performance.

  17. Influence of aging on membrane permeability transition in brain mitochondria.

    PubMed

    Toman, Julia; Fiskum, Gary

    2011-02-01

    The mitochondrial inner membrane permeability transition (MPT) plays an important role in the pathophysiology of acute disorders of the central nervous systems, including ischemic and traumatic brain injury, and possibly in neurodegenerative diseases. Opening of the permeability transition pore (PTP) by a combination of abnormally elevated intramitochondrial Ca2+ and oxidative stress induces the collapse of transmembrane ion gradients, resulting in membrane depolarization and uncoupling of oxidative phosphorylation. This loss of ATP synthesis eventually results in cellular metabolic failure and necrotic cell death. Drugs, e.g., cyclosporin A, can inhibit the permeability transition through their interaction with the mitochondria-specific protein, cyclophilin D, and demonstrate neuroprotection in several animal models. These characteristics of the MPT were developed almost exclusively from experiments performed with young, mature rodents whereas the neuropathologies associated with the MPT are most prevalent in the elderly population. Some evidence indicates that the sensitivity of mitochondria to Ca2+-induced PTP opening is greater in the aged compared to the young mature brain; however, the basis for this difference is unknown. Based on knowledge of factors that regulate the MPT and on other comparisons between cells and mitochondria from young and old animals, several features may be important. These aging-related features include impaired neuronal Ca2+ homeostasis, increased oxidative stress, increased cyclophilin D protein levels, oxidative modification of the adenine nucleotide translocase and of cardiolipin, and changes in the levels of anti-death mitochondrial proteins, e.g., Bcl-2. The influence of aging on both the contribution of the MPT to neuropathology and the neuroprotective efficacy of MPT inhibitors is a substantial knowledge gap that requires extensive research at the subcellular, cellular, and animal model levels.

  18. Evidence of accelerated aging among African Americans and its implications for mortality.

    PubMed

    Levine, M E; Crimmins, E M

    2014-10-01

    Blacks experience morbidity and mortality earlier in the life course compared to whites. Such premature declines in health may be indicative of an acceleration of the aging process. The current study uses data on 7644 black and white participants, ages 30 and above, from the third National Health and Nutrition Examination Survey, to compare the biological ages of blacks and whites as indicated from a combination of ten biomarkers and to determine if such differences in biological age relative to chronological age account for racial disparities in mortality. At a specified chronological age, blacks are approximately 3 years older biologically than whites. Differences in biological age between blacks and whites appear to increase up until ages 60-65 and then decline, presumably due to mortality selection. Finally, differences in biological age were found to completely account for higher levels of all-cause, cardiovascular and cancer mortality among blacks. Overall, these results suggest that being black is associated with significantly higher biological age at a given chronological age and that this is a pathway to early death both overall and from the major age-related diseases.

  19. Accelerated aging in schizophrenia patients: the potential role of oxidative stress.

    PubMed

    Okusaga, Olaoluwa O

    2014-08-01

    Several lines of evidence suggest that schizophrenia, a severe mental illness characterized by delusions, hallucinations and thought disorder is associated with accelerated aging. The free radical (oxidative stress) theory of aging assumes that aging occurs as a result of damage to cell constituents and connective tissues by free radicals arising from oxygen-associated reactions. Schizophrenia has been associated with oxidative stress and chronic inflammation, both of which also appear to reciprocally induce each other in a positive feedback manner. The buildup of damaged macromolecules due to increased oxidative stress and failure of protein repair and maintenance systems is an indicator of aging both at the cellular and organismal level. When compared with age-matched healthy controls, schizophrenia patients have higher levels of markers of oxidative cellular damage such as protein carbonyls, products of lipid peroxidation and DNA hydroxylation. Potential confounders such as antipsychotic medication, smoking, socio-economic status and unhealthy lifestyle make it impossible to solely attribute the earlier onset of aging-related changes or oxidative stress to having a diagnosis of schizophrenia. Regardless of whether oxidative stress can be attributed solely to a diagnosis of schizophrenia or whether it is due to other factors associated with schizophrenia, the available evidence is in support of increased oxidative stress-induced cellular damage of macromolecules which may play a role in the phenomenon of accelerated aging presumed to be associated with schizophrenia.

  20. Accelerated Aging in Schizophrenia Patients: The Potential Role of Oxidative Stress

    PubMed Central

    Okusaga, Olaoluwa O

    2014-01-01

    Several lines of evidence suggest that schizophrenia, a severe mental illness characterized by delusions, hallucinations and thought disorder is associated with accelerated aging. The free radical (oxidative stress) theory of aging assumes that aging occurs as a result of damage to cell constituents and connective tissues by free radicals arising from oxygen-associated reactions. Schizophrenia has been associated with oxidative stress and chronic inflammation, both of which also appear to reciprocally induce each other in a positive feedback manner. The buildup of damaged macromolecules due to increased oxidative stress and failure of protein repair and maintenance systems is an indicator of aging both at the cellular and organismal level. When compared with age-matched healthy controls, schizophrenia patients have higher levels of markers of oxidative cellular damage such as protein carbonyls, products of lipid peroxidation and DNA hydroxylation. Potential confounders such as antipsychotic medication, smoking, socio-economic status and unhealthy lifestyle make it impossible to solely attribute the earlier onset of aging-related changes or oxidative stress to having a diagnosis of schizophrenia. Regardless of whether oxidative stress can be attributed solely to a diagnosis of schizophrenia or whether it is due to other factors associated with schizophrenia, the available evidence is in support of increased oxidative stress-induced cellular damage of macromolecules which may play a role in the phenomenon of accelerated aging presumed to be associated with schizophrenia. PMID:25110609

  1. Prion protein accumulation in lipid rafts of mouse aging brain.

    PubMed

    Agostini, Federica; Dotti, Carlos G; Pérez-Cañamás, Azucena; Ledesma, Maria Dolores; Benetti, Federico; Legname, Giuseppe

    2013-01-01

    The cellular form of the prion protein (PrP(C)) is a normal constituent of neuronal cell membranes. The protein misfolding causes rare neurodegenerative disorders known as transmissible spongiform encephalopathies or prion diseases. These maladies can be sporadic, genetic or infectious. Sporadic prion diseases are the most common form mainly affecting aging people. In this work, we investigate the biochemical environment in which sporadic prion diseases may develop, focusing our attention on the cell membrane of neurons in the aging brain. It is well established that with aging the ratio between the most abundant lipid components of rafts undergoes a major change: while cholesterol decreases, sphingomyelin content rises. Our results indicate that the aging process modifies the compartmentalization of PrP(C). In old mice, this change favors PrP(C) accumulation in detergent-resistant membranes, particularly in hippocampi. To confirm the relationship between lipid content changes and PrP(C) translocation into detergent-resistant membranes (DRMs), we looked at PrP(C) compartmentalization in hippocampi from acid sphingomyelinase (ASM) knockout (KO) mice and synaptosomes enriched in sphingomyelin. In the presence of high sphingomyelin content, we observed a significant increase of PrP(C) in DRMS. This process is not due to higher levels of total protein and it could, in turn, favor the onset of sporadic prion diseases during aging as it increases the PrP intermolecular contacts into lipid rafts. We observed that lowering sphingomyelin in scrapie-infected cells by using fumonisin B1 led to a 50% decrease in protease-resistant PrP formation. This may suggest an involvement of PrP lipid environment in prion formation and consequently it may play a role in the onset or development of sporadic forms of prion diseases.

  2. Prion Protein Accumulation in Lipid Rafts of Mouse Aging Brain

    PubMed Central

    Agostini, Federica; Dotti, Carlos G.; Pérez-Cañamás, Azucena; Ledesma, Maria Dolores; Benetti, Federico; Legname, Giuseppe

    2013-01-01

    The cellular form of the prion protein (PrPC) is a normal constituent of neuronal cell membranes. The protein misfolding causes rare neurodegenerative disorders known as transmissible spongiform encephalopathies or prion diseases. These maladies can be sporadic, genetic or infectious. Sporadic prion diseases are the most common form mainly affecting aging people. In this work, we investigate the biochemical environment in which sporadic prion diseases may develop, focusing our attention on the cell membrane of neurons in the aging brain. It is well established that with aging the ratio between the most abundant lipid components of rafts undergoes a major change: while cholesterol decreases, sphingomyelin content rises. Our results indicate that the aging process modifies the compartmentalization of PrPC. In old mice, this change favors PrPC accumulation in detergent-resistant membranes, particularly in hippocampi. To confirm the relationship between lipid content changes and PrPC translocation into detergent-resistant membranes (DRMs), we looked at PrPC compartmentalization in hippocampi from acid sphingomyelinase (ASM) knockout (KO) mice and synaptosomes enriched in sphingomyelin. In the presence of high sphingomyelin content, we observed a significant increase of PrPC in DRMS. This process is not due to higher levels of total protein and it could, in turn, favor the onset of sporadic prion diseases during aging as it increases the PrP intermolecular contacts into lipid rafts. We observed that lowering sphingomyelin in scrapie-infected cells by using fumonisin B1 led to a 50% decrease in protease-resistant PrP formation. This may suggest an involvement of PrP lipid environment in prion formation and consequently it may play a role in the onset or development of sporadic forms of prion diseases. PMID:24040215

  3. Predicting brain-age from multimodal imaging data captures cognitive impairment.

    PubMed

    Liem, Franziskus; Varoquaux, Gaël; Kynast, Jana; Beyer, Frauke; Kharabian Masouleh, Shahrzad; Huntenburg, Julia M; Lampe, Leonie; Rahim, Mehdi; Abraham, Alexandre; Craddock, R Cameron; Riedel-Heller, Steffi; Luck, Tobias; Loeffler, Markus; Schroeter, Matthias L; Witte, Anja Veronica; Villringer, Arno; Margulies, Daniel S

    2017-03-01

    The disparity between the chronological age of an individual and their brain-age measured based on biological information has the potential to offer clinically relevant biomarkers of neurological syndromes that emerge late in the lifespan. While prior brain-age prediction studies have relied exclusively on either structural or functional brain data, here we investigate how multimodal brain-imaging data improves age prediction. Using cortical anatomy and whole-brain functional connectivity on a large adult lifespan sample (N=2354, age 19-82), we found that multimodal data improves brain-based age prediction, resulting in a mean absolute prediction error of 4.29 years. Furthermore, we found that the discrepancy between predicted age and chronological age captures cognitive impairment. Importantly, the brain-age measure was robust to confounding effects: head motion did not drive brain-based age prediction and our models generalized reasonably to an independent dataset acquired at a different site (N=475). Generalization performance was increased by training models on a larger and more heterogeneous dataset. The robustness of multimodal brain-age prediction to confounds, generalizability across sites, and sensitivity to clinically-relevant impairments, suggests promising future application to the early prediction of neurocognitive disorders.

  4. Hypercholesterolemia Induces Oxidant Stress That Accelerates the Ageing of Hematopoietic Stem Cells

    PubMed Central

    Tie, Guodong; Messina, Katharine E.; Yan, Jinglian; Messina, Julia A.; Messina, Louis M.

    2014-01-01

    Background Clinical studies suggest that hypercholesterolemia may cause ageing in hematopoietic stem cells (HSCs) because ageing‐associated alterations were found in peripheral blood cells and their bone marrow residing precursors in patients with advanced atherosclerosis. We hypothesized that hypercholesterolemia induces oxidant stress in hematopoietic stems cells that accelerates their ageing. Methods and Results Here we show that HSCs from ApoE−/− mice, as well as HSCs from C57Bl/6 mice fed a high cholesterol diet (HCD) accumulated oxLDL and had greater ROS levels. In accordance, the expression pattern of the genes involved in ROS metabolism changed significantly in HSCs from ApoE−/− mice. Hypercholesterolemia caused a significant reduction in phenotypically defined long‐term HSC compartment, telomere length, and repopulation capacity of KTLS cells, indicating accelerated ageing in these cells. Gene array analysis suggested abnormal cell cycle status, and the key cell cycle regulators including p19ARF, p27Kip1 and p21Waf1 were upregulated in KTLS cells from hypercholesterolemic mice. These effects were p38‐dependent and reversed in vivo by treatment of hypercholesterolemic mice with antioxidant N‐acetylcysteine. The oxidant stress also caused aberrant expression of Notch1 that caused loss of quiescence and proliferation leading to the expansion of KTLS compartment in hypercholesterolemic mice. Conclusion Taken together, we provide evidence that hypercholesterolemia can cause oxidant stress that accelerates the ageing and impairs the reconstitution capacity of HSCs. PMID:24470519

  5. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice

    PubMed Central

    Zhang, Yiqiang; Fischer, Kathleen E.; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B.

    2015-01-01

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality leading some to suggest this represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased in high fat-fed mice as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. PMID:25558793

  6. Acceleration of cardiovascular-biological age by amphetamine exposure is a power function of chronological age

    PubMed Central

    Norman, Amanda; Hulse, Gary Kenneth

    2017-01-01

    Background Amphetamine abuse is becoming more widespread internationally. The possibility that its many cardiovascular complications are associated with a prematurely aged cardiovascular system, and indeed biological organism systemically, has not been addressed. Methods Radial arterial pulse tonometry was performed using the SphygmoCor system (Sydney). 55 amphetamine exposed patients were compared with 107 tobacco smokers, 483 non-smokers and 68 methadone patients (total=713 patients) from 2006 to 2011. A cardiovascular-biological age (VA) was determined. Results The age of the patient groups was 30.03±0.51–40.45±1.15 years. This was controlled for with linear regression. The sex ratio was the same in all groups. 94% of amphetamine exposed patients had used amphetamine in the previous week. When the (log) VA was regressed against the chronological age (CA) and a substance-type group in both cross-sectional and longitudinal models, models quadratic in CA were superior to linear models (both p<0.02). When log VA/CA was regressed in a mixed effects model against time, body mass index, CA and drug type, the cubic model was superior to the linear model (p=0.001). Interactions between CA, (CA)2 and (CA)3 on the one hand and exposure type were significant from p=0.0120. The effects of amphetamine exposure persisted after adjustment for all known cardiovascular risk factors (p<0.0001). Conclusions These results show that subacute exposure to amphetamines is associated with an advancement of cardiovascular-organismal age both over age and over time, and is robust to adjustment. That this is associated with power functions of age implies a feed-forward positively reinforcing exacerbation of the underlying ageing process. PMID:28243315

  7. Neuronutrient impact of Ayurvedic Rasayana therapy in brain aging.

    PubMed

    Singh, Ram Harsh; Narsimhamurthy, K; Singh, Girish

    2008-12-01

    Ayurveda is the oldest system of Medicine in the world, its antiquity going back to the Vedas. It adapts a unique holistic approach to the entire science of life, health and cure. The areas of special consideration in Ayurveda are geriatrics, rejuvenation, nutrition, immunology, genetics and higher consciousness. The Ayurvedic texts describe a set of rejuvenative measures to impart biological sustenance to the bodily tissues. These remedies are called Rasayana which are claimed to act as micronutrients. Some of these Rasayanas are organ and tissue specific. Those specific to brain tissue are called Medhya Rasayana. Such Rasayanas retard brain aging and help in regeneration of neural tissues besides producing antistress, adaptogenic and memory enhancing effect. In addition to the long tradition of textual and experience-based evidence for their efficacy, certain recent studies conducted on these traditional remedies on scientific parameters have shown promising results which have been reviewed in this paper for providing lead for further studies. The popular Medhya Rasayanas are Ashwagandha (Withania somnifera Dunal), Brahmi (Bacopa monnieri Linn), Mandukaparni (Centella asiatica Linn) and Sankhapuspi (Convolvulus pluricaulis Chois).

  8. 1,3-dinitrobenzene induces age- and region-specific oxidation to mitochondria-related proteins in brain.

    PubMed

    Kubik, Laura L; Landis, Rory W; Remmer, Henriette; Bergin, Ingrid L; Philbert, Martin A

    2015-05-01

    Regions of the brain with high energy requirements are especially sensitive to perturbations in mitochondrial function. Hence, neurotoxicant exposures that target mitochondria in regions of high energy demand have the potential to accelerate mitochondrial damage inherently occurring during the aging process. 1,3-Dinitrobenzene (DNB) is a model neurotoxicant that selectively targets mitochondria in brainstem nuclei innervated by the eighth cranial nerve. This study investigates the role of age in the regional susceptibility of brain mitochondria-related proteins (MRPs) to oxidation following exposure to DNB. Male F344 rats (1 month old [young], 3 months old [adult], 18 months old [aged]) were exposed to 10 mg/kg DNB prior to mitochondrial isolation and histopathology experiments. Using a high-throughput proteomic approach, 3 important region- and age-related increases in DNB-induced MRP oxidation were determined: (1) brainstem mitochondria are ×3 more sensitive to DNB-induced oxidation than cortical mitochondria; (2) oxidation of brainstem MRPs is significantly higher than in cortical counterparts; and (3) MRPs from the brainstems of older rats are significantly more oxidized than those from young or adult rats. Furthermore, lower levels of DNB cause signs of intoxication (ataxia, chromodacryorrhea) and vacuolation of the susceptible neuropil in aged animals, while neither is observed in DNB-exposed young rats. Additionally, methemoglobin levels increase significantly in DNB-exposed adult and aged animals, but not young DNB-exposed animals. This suggests that oxidation of key MRPs observed in brainstem of aged animals is necessary for DNB-induced signs of intoxication and lesion formation. These results provide compelling evidence that environmental chemicals such as DNB may aid in the acceleration of injury to specific brain regions by inducing oxidation of sensitive mitochondrial proteins.

  9. Alzheimer risk variant CLU and brain function during aging

    PubMed Central

    Thambisetty, Madhav; Beason-Held, Lori L.; An, Yang; Kraut, Michael; Nalls, Michael; Hernandez, Dena G.; Singleton, Andrew B.; Zonderman, Alan B.; Ferrucci, Luigi; Lovestone, Simon; Resnick, Susan M.

    2012-01-01

    Background We examined the effect of the novel Alzheimer's disease (AD) risk variant rs11136000 single nucleotide polymorphism (SNP) in the clusterin gene (CLU) on longitudinal changes in resting state regional cerebral blood flow (rCBF) during normal aging and investigated its influence on cognitive decline in pre-symptomatic stages of disease progression. Methods Subjects were participants in the Baltimore Longitudinal Study of Aging. A subset of 88 cognitively normal older individuals had longitudinal 15O-water PET measurements of rCBF at baseline and up to 8 annual follow-up visits. We also analyzed trajectories of cognitive decline among CLU risk carriers and non-carriers both in individuals who remained cognitively normal (N=599) as well as in those who subsequently converted to mild cognitive impairment (MCI) or AD (N=95). Results Cognitively normal carriers of the CLU risk allele show significant and dose-dependent longitudinal increases in resting state rCBF in brain regions intrinsic to memory processes. There were no differences in trajectories of memory performance between CLU risk carriers and non-carriers who remained cognitively normal. However, in cognitively normal individuals who eventually convert to MCI or AD, CLU risk carriers show faster rates of decline in memory performance relative to non-carriers in the pre-symptomatic stages of disease progression. Conclusions The AD risk variant CLU influences longitudinal changes in brain function in asymptomatic individuals and is associated with faster cognitive decline in pre-symptomatic stages of disease progression. These results suggest mechanisms underlying the role of CLU in AD and may be important in monitoring disease progression in at-risk elderly. PMID:22795969

  10. Arsenite exposure accelerates aging process regulated by the transcription factor DAF-16/FOXO in Caenorhabditis elegans.

    PubMed

    Yu, Chan-Wei; How, Chun Ming; Liao, Vivian Hsiu-Chuan

    2016-05-01

    Arsenic is a known human carcinogen and high levels of arsenic contamination in food, soils, water, and air are of toxicology concerns. Nowadays, arsenic is still a contaminant of emerging interest, yet the effects of arsenic on aging process have received little attention. In this study, we investigated the effects and the underlying mechanisms of chronic arsenite exposure on the aging process in Caenorhabditis elegans. The results showed that prolonged arsenite exposure caused significantly decreased lifespan compared to non-exposed ones. In addition, arsenite exposure (100 μM) caused significant changes of age-dependent biomarkers, including a decrease of defecation frequency, accumulations of intestinal lipofuscin and lipid peroxidation in an age-dependent manner in C. elegans. Further evidence revealed that intracellular reactive oxygen species (ROS) level was significantly increased in an age-dependent manner upon 100 μM arsenite exposure. Moreover, the mRNA levels of transcriptional makers of aging (hsp-16.1, hsp-16.49, and hsp-70) were increased in aged worms under arsenite exposure (100 μM). Finally, we showed that daf-16 mutant worms were more sensitive to arsenite exposure (100 μM) on lifespan and failed to induce the expression of its target gene sod-3 in aged daf-16 mutant under arsenite exposure (100 μM). Our study demonstrated that chronic arsenite exposure resulted in accelerated aging process in C. elegans. The overproduction of intracellular ROS and the transcription factor DAF-16/FOXO play roles in mediating the accelerated aging process by arsenite exposure in C. elegans. This study implicates a potential ecotoxicological and health risk of arsenic in the environment.

  11. High-field proton magnetic resonance spectroscopy reveals metabolic effects of normal brain aging.

    PubMed

    Harris, Janna L; Yeh, Hung-Wen; Swerdlow, Russell H; Choi, In-Young; Lee, Phil; Brooks, William M

    2014-07-01

    Altered brain metabolism is likely to be an important contributor to normal cognitive decline and brain pathology in elderly individuals. To characterize the metabolic changes associated with normal brain aging, we used high-field proton magnetic resonance spectroscopy in vivo to quantify 20 neurochemicals in the hippocampus and sensorimotor cortex of young adult and aged rats. We found significant differences in the neurochemical profile of the aged brain when compared with younger adults, including lower aspartate, ascorbate, glutamate, and macromolecules, and higher glucose, myo-inositol, N-acetylaspartylglutamate, total choline, and glutamine. These neurochemical biomarkers point to specific cellular mechanisms that are altered in brain aging, such as bioenergetics, oxidative stress, inflammation, cell membrane turnover, and endogenous neuroprotection. Proton magnetic resonance spectroscopy may be a valuable translational approach for studying mechanisms of brain aging and pathology, and for investigating treatments to preserve or enhance cognitive function in aging.

  12. Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe?

    PubMed Central

    Nunn, Alistair VW; Bell, Jimmy D; Guy, Geoffrey W

    2009-01-01

    determines functional longevity, a rather more descriptive term for the metabolic syndrome is the 'lifestyle-induced metabolic inflexibility and accelerated ageing syndrome'. Ultimately, thriftiness is good for us as long as we have hormetic stimuli; unfortunately, mankind is attempting to remove all hormetic (stressful) stimuli from his environment. PMID:19371409

  13. Spectroscopic characterization of the oligomeric surface structures on polyamide materials formed during accelerated aging.

    PubMed

    Chernev, Boril S; Eder, Gabriele C

    2011-10-01

    Crystalline surface species were observed at the surface of polyamide 12 materials upon accelerated aging. After detection of the depositions with scanning electron microscopy (SEM), the crystalline surface precipitations were analyzed with Fourier transform infrared (FT-IR) and Raman imaging microscopy. These surface species were supposed to be cyclic oligomers (dimer and trimer) of the PA12 monomer laurolactam, which are usually present in polyamide materials and tend to migrate to the surface when the material is subjected to accelerated aging. The evidence for the chemical identity of the crystalline surface structures to be mainly the cyclic dimer and trimer of laurolactam was given by melting-point identification and mass spectroscopic analysis of the methanol eluate of the surface. The Raman and FT-IR spectra of the mixture were extracted from the recorded images.

  14. Colour stability of temporary restorations with different thicknesses submitted to artificial accelerated aging.

    PubMed

    Silame, F D J; Tonani, R; Alandia-Roman, C C; Chinelatti, M; Panzeri, H; Pires-de-Souza, F C P

    2013-12-01

    This study evaluated the colour stability of temporary prosthetic restorations with different thicknesses submitted to artificial accelerated aging. The occlusal surfaces of 40 molars were grinded to obtain flat enamel surfaces. Twenty acrylic resin specimens [Polymethyl methacrylate (Duralay) and Bis-methyl acrylate (Luxatemp)] were made with two different thicknesses, 0.5 mm and 1.0 mm. Temporary restorations were fixed on enamel and CIE L*a*b* colour parameters of each specimen were assessed before and after artificial accelerated aging. All groups showed colour alterations above the clinically acceptable limit. Luxatemp showed the lowest colour alteration regardless its thickness and Duralay showed the greatest alteration with 0.5 mm.

  15. A hybrid CPU-GPU accelerated framework for fast mapping of high-resolution human brain connectome.

    PubMed

    Wang, Yu; Du, Haixiao; Xia, Mingrui; Ren, Ling; Xu, Mo; Xie, Teng; Gong, Gaolang; Xu, Ningyi; Yang, Huazhong; He, Yong

    2013-01-01

    Recently, a combination of non-invasive neuroimaging techniques and graph theoretical approaches has provided a unique opportunity for understanding the patterns of the structural and functional connectivity of the human brain (referred to as the human brain connectome). Currently, there is a very large amount of brain imaging data that have been collected, and there are very high requirements for the computational capabilities that are used in high-resolution connectome research. In this paper, we propose a hybrid CPU-GPU framework to accelerate the computation of the human brain connectome. We applied this framework to a publicly available resting-state functional MRI dataset from 197 participants. For each subject, we first computed Pearson's Correlation coefficient between any pairs of the time series of gray-matter voxels, and then we constructed unweighted undirected brain networks with 58 k nodes and a sparsity range from 0.02% to 0.17%. Next, graphic properties of the functional brain networks were quantified, analyzed and compared with those of 15 corresponding random networks. With our proposed accelerating framework, the above process for each network cost 80∼150 minutes, depending on the network sparsity. Further analyses revealed that high-resolution functional brain networks have efficient small-world properties, significant modular structure, a power law degree distribution and highly connected nodes in the medial frontal and parietal cortical regions. These results are largely compatible with previous human brain network studies. Taken together, our proposed framework can substantially enhance the applicability and efficacy of high-resolution (voxel-based) brain network analysis, and have the potential to accelerate the mapping of the human brain connectome in normal and disease states.

  16. On the Use of Accelerated Aging Methods for Screening High Temperature Polymeric Composite Materials

    NASA Technical Reports Server (NTRS)

    Gates, Thomas S.; Grayson, Michael A.

    1999-01-01

    A rational approach to the problem of accelerated testing of high temperature polymeric composites is discussed. The methods provided are considered tools useful in the screening of new materials systems for long-term application to extreme environments that include elevated temperature, moisture, oxygen, and mechanical load. The need for reproducible mechanisms, indicator properties, and real-time data are outlined as well as the methodologies for specific aging mechanisms.

  17. Does cyclic stress and accelerated ageing influence the wear behavior of highly crosslinked polyethylene?

    PubMed

    Affatato, Saverio; De Mattia, Jonathan Salvatore; Bracco, Pierangiola; Pavoni, Eleonora; Taddei, Paola

    2016-06-01

    First-generation (irradiated and remelted or annealed) and second-generation (irradiated and vitamin E blended or doped) highly crosslinked polyethylenes were introduced in the last decade to solve the problems of wear and osteolysis. In this study, the influence of the Vitamin-E addition on crosslinked polyethylene (XLPE_VE) was evaluated by comparing the in vitro wear behavior of crosslinked polyethylene (XLPE) versus Vitamin-E blended polyethylene XLPE and conventional ultra-high molecular weight polyethylene (STD_PE) acetabular cups, after accelerated ageing according to ASTM F2003-02 (70.0±0.1°C, pure oxygen at 5bar for 14 days). The test was performed using a hip joint simulator run for two millions cycles, under bovine calf serum as lubricant. Mass loss was found to decrease along the series XLPE_VE>STD_PE>XLPE, although no statistically significant differences were found between the mass losses of the three sets of cups. Micro-Raman spectroscopy was used to investigate at a molecular level the morphology changes induced by wear. The spectroscopic analyses showed that the accelerated ageing determined different wear mechanisms and molecular rearrangements during testing with regards to the changes in both the chain orientation and the distribution of the all-trans sequences within the orthorhombic, amorphous and third phases. The results of the present study showed that the addition of vitamin E was not effective to improve the gravimetric wear of PE after accelerated ageing. However, from a molecular point of view, the XLPE_VE acetabular cups tested after accelerated ageing appeared definitely less damaged than the STD_PE ones and comparable to XLPE samples.

  18. Chromatic stability of acrylic resins of artificial eyes submitted to accelerated aging and polishing

    PubMed Central

    GOIATO, Marcelo Coelho; dos SANTOS, Daniela Micheline; SOUZA, Josiene Firmino; MORENO, Amália; PESQUEIRA, Aldiéris Alves

    2010-01-01

    Esthetics and durability of materials used to fabricate artificial eyes has been an important eissue since artificial eyes are essential to restore esthetics and function, protect the remaining tissues and help with patients' psychological therapy. However, these materials are submitted to degrading effects of environmental agents on the physical properties of the acrylic resin. Objective This study assessed the color stability of acrylic resins used to fabricate sclera in three basic shades (N1, N2 and N3) when subjected to accelerated aging, mechanical and chemical polishing. Material and methods Specimens of each resin were fabricated and submitted to mechanical and chemical polishing. Chromatic analysis was performed before and after accelerated aging through ultraviolet reflection spectrophotometry. Results All specimens revealed color alteration following polishing and accelerated aging. The resins presented statistically significant chromatic alteration (p<0.01) between the periods of 252 and 1008 h. Conclusions Both polishing methods presented no significant difference between the values of color derivatives of resins. PMID:21308298

  19. Montefiore-Einstein Center for the Aging Brain: Preliminary Data.

    PubMed

    Verghese, Joe; Malik, Rubina; Zwerling, Jessica

    2016-11-01

    Given the multifaceted nature of dementia care management, an interdisciplinary comprehensive clinical approach is necessary. We describe our one-year experience with outpatient based dementia care at the Montefiore-Einstein Center for the Aging Brain (CAB) involving an multispecialty team of geriatricians, neurologists, and neuropsychologists, supported by geriatric psychiatrists, physiatrists, and social services. The goals of the CAB is to maximize dementia outcomes, including regular monitoring of patient's health and cognition, education and support to patients, their families and caregivers; initiation of pharmacological and non-pharmacological treatments as appropriate, and the facilitation of access to clinical trials. The CAB follows a consultative model where patients referred to the center receive a comprehensive three step evaluation and management plan from Geriatric, Neuropsychology and Neurology specialists that is shared with patient, caregivers and primary care physicians. Of the 366 patients seen for cognitive complaints in our first year, 71% were women with a mean age of 74 years. Self-identified ethnicity of patients included Caucasian (26%), African-American (25%), Hispanic (18%) and multiracial (5%). Common final diagnoses assigned at the CAB included mild cognitive impairment syndromes (31%), Alzheimer's disease (20%), mixed dementia (11%), vascular dementia (9%), Frontotemporal dementia (4%) and dementia with Lewy bodies (4%). Our one-year progress report indicates that an interdisciplinary clinical dementia care model is feasible in the outpatient setting as well as highly accepted by patients, caregivers and referring physicians.

  20. Service Lifetime Estimation of EPDM Rubber Based on Accelerated Aging Tests

    NASA Astrophysics Data System (ADS)

    Liu, Jie; Li, Xiangbo; Xu, Likun; He, Tao

    2017-02-01

    Service lifetime of ethylene propylene diene monomer (EPDM) rubber at room temperature (25 °C) was estimated based on accelerated aging tests. The study followed sealing stress loss on compressed cylinder samples by compression stress relaxation methods. The results showed that the cylinder samples of EPDM can quickly reach the physical relaxation equilibrium by using the over-compression method. The non-Arrhenius behavior occurred at the lowest aging temperature. A significant linear relationship was observed between compression set values and normalized stress decay results, and the relationship was not related to the ambient temperature of aging. It was estimated that the sealing stress loss in view of practical application would occur after around 86.8 years at 25 °C. The estimations at 25 °C based on the non-Arrhenius behavior were in agreement with compression set data from storage aging tests in natural environment.

  1. Do US Black Women Experience Stress-Related Accelerated Biological Aging?

    PubMed Central

    Hicken, Margaret T.; Pearson, Jay A.; Seashols, Sarah J.; Brown, Kelly L.; Cruz, Tracey Dawson

    2010-01-01

    We hypothesize that black women experience accelerated biological aging in response to repeated or prolonged adaptation to subjective and objective stressors. Drawing on stress physiology and ethnographic, social science, and public health literature, we lay out the rationale for this hypothesis. We also perform a first population-based test of its plausibility, focusing on telomere length, a biomeasure of aging that may be shortened by stressors. Analyzing data from the Study of Women's Health Across the Nation (SWAN), we estimate that at ages 49–55, black women are 7.5 years biologically “older” than white women. Indicators of perceived stress and poverty account for 27% of this difference. Data limitations preclude assessing objective stressors and also result in imprecise estimates, limiting our ability to draw firm inferences. Further investigation of black-white differences in telomere length using large-population-based samples of broad age range and with detailed measures of environmental stressors is merited. PMID:20436780

  2. Proposition of an Accelerated Ageing Method for Natural Fibre/Polylactic Acid Composite

    NASA Astrophysics Data System (ADS)

    Zandvliet, Clio; Bandyopadhyay, N. R.; Ray, Dipa

    2015-10-01

    Natural fibre composite based on polylactic acid (PLA) composite is of special interest because it is entirely from renewable resources and biodegradable. Some samples of jute/PLA composite and PLA alone made 6 years ago and kept in tropical climate on a shelf shows too fast ageing degradation. In this work, an accelerated ageing method for natural fibres/PLA composite is proposed and tested. Experiment was carried out with jute and flax fibre/PLA composite. The method was compared with the standard ISO 1037-06a. The residual flexural strength after ageing test was compared with the one of common wood-based panels and of real aged samples prepared 6 years ago.

  3. Accelerated features of age-related bone loss in zmpste24 metalloproteinase-deficient mice.

    PubMed

    Rivas, Daniel; Li, Wei; Akter, Rahima; Henderson, Janet E; Duque, Gustavo

    2009-10-01

    Age-related bone loss is associated with changes in bone cellularity, which include marrow fat infiltration and decreasing levels of osteoblastogenesis. The mechanisms that explain these changes remain unclear. Although nuclear lamina alterations occur in premature aging syndromes that include changes in body fat and severe osteoporosis, the role of proteins of the nuclear lamina in age-related bone loss remains unknown. Using the Zmpste24-null progeroid mice (Zmpste24(-/-)), which exhibit nuclear lamina defects and accumulate unprocessed prelamin A, we identified several alterations in bone cellularity in vivo. We found that defective prelamin A processing induced accelerated features of age-related bone loss including lower osteoblast and osteocyte numbers and higher levels of marrow adipogenesis. In summary, processing of prelamin A could become a new approach to regulate osteoblastogenesis and bone turnover and thus for the prevention and treatment of senile osteoporosis.

  4. Effects of incentives, age, and behavior on brain activation during inhibitory control: a longitudinal fMRI study.

    PubMed

    Paulsen, David J; Hallquist, Michael N; Geier, Charles F; Luna, Beatriz

    2015-02-01

    We investigated changes in brain function supporting inhibitory control under age-controlled incentivized conditions, separating age- and performance-related activation in an accelerated longitudinal design including 10- to 22-year-olds. Better inhibitory control correlated with striatal activation during neutral trials, while Age X Behavior interactions in the striatum indicated that in the absence of extrinsic incentives, younger subjects with greater reward circuitry activation successfully engage in greater inhibitory control. Age was negatively correlated with ventral amygdala activation during Loss trials, suggesting that amygdala function more strongly mediates bottom-up processing earlier in development when controlling the negative aspects of incentives to support inhibitory control. Together, these results indicate that with development, reward-modulated cognitive control may be supported by incentive processing transitions in the amygdala, and from facilitative to obstructive striatal function during inhibitory control.

  5. Angular Impact Mitigation System for Bicycle Helmets to Reduce Head Acceleration and Risk of Traumatic Brain Injury

    PubMed Central

    Hansen, Kirk; Dau, Nathan; Feist, Florian; Deck, Caroline; Willinger, Rémy; Madey, Steven M.; Bottlang, Michael

    2013-01-01

    Angular acceleration of the head is a known cause of traumatic brain injury (TBI), but contemporary bicycle helmets lack dedicated mechanisms to mitigate angular acceleration. A novel Angular Impact Mitigation (AIM) system for bicycle helmets has been developed that employs an elastically suspended aluminum honeycomb liner to absorb linear acceleration in normal impacts as well as angular acceleration in oblique impacts. This study tested bicycle helmets with and without AIM technology to comparatively assess impact mitigation. Normal impact tests were performed to measure linear head acceleration. Oblique impact tests were performed to measure angular head acceleration and neck loading. Furthermore, acceleration histories of oblique impacts were analyzed in a computational head model to predict the resulting risk of TBI in the form of concussion and diffuse axonal injury (DAI). Compared to standard helmets, AIM helmets resulted in a 14% reduction in peak linear acceleration (p < 0.001), a 34% reduction in peak angular acceleration (p < 0.001), and a 22% to 32% reduction in neck loading (p < 0.001). Computational results predicted that AIM helmets reduced the risk of concussion and DAI by 27% and 44%, respectively. In conclusion, these results demonstrated that AIM technology could effectively improve impact mitigation compared to a contemporary expanded polystyrene-based bicycle helmet, and may enhance prevention of bicycle-related TBI. Further research is required. PMID:23770518

  6. Angular Impact Mitigation system for bicycle helmets to reduce head acceleration and risk of traumatic brain injury.

    PubMed

    Hansen, Kirk; Dau, Nathan; Feist, Florian; Deck, Caroline; Willinger, Rémy; Madey, Steven M; Bottlang, Michael

    2013-10-01

    Angular acceleration of the head is a known cause of traumatic brain injury (TBI), but contemporary bicycle helmets lack dedicated mechanisms to mitigate angular acceleration. A novel Angular Impact Mitigation (AIM) system for bicycle helmets has been developed that employs an elastically suspended aluminum honeycomb liner to absorb linear acceleration in normal impacts as well as angular acceleration in oblique impacts. This study tested bicycle helmets with and without AIM technology to comparatively assess impact mitigation. Normal impact tests were performed to measure linear head acceleration. Oblique impact tests were performed to measure angular head acceleration and neck loading. Furthermore, acceleration histories of oblique impacts were analyzed in a computational head model to predict the resulting risk of TBI in the form of concussion and diffuse axonal injury (DAI). Compared to standard helmets, AIM helmets resulted in a 14% reduction in peak linear acceleration (p<0.001), a 34% reduction in peak angular acceleration (p<0.001), and a 22-32% reduction in neck loading (p<0.001). Computational results predicted that AIM helmets reduced the risk of concussion and DAI by 27% and 44%, respectively. In conclusion, these results demonstrated that AIM technology could effectively improve impact mitigation compared to a contemporary expanded polystyrene-based bicycle helmet, and may enhance prevention of bicycle-related TBI. Further research is required.

  7. Tooth loss early in life accelerates age-related bone deterioration in mice.

    PubMed

    Kurahashi, Minori; Kondo, Hiroko; Iinuma, Mitsuo; Tamura, Yasuo; Chen, Huayue; Kubo, Kin-ya

    2015-01-01

    Both osteoporosis and tooth loss are health concerns that affect many older people. Osteoporosis is a common skeletal disease of the elderly, characterized by low bone mass and microstructural deterioration of bone tissue. Chronic mild stress is a risk factor for osteoporosis. Many studies showed that tooth loss induced neurological alterations through activation of a stress hormone, corticosterone, in mice. In this study, we tested the hypothesis that tooth loss early in life may accelerate age-related bone deterioration using a mouse model. Male senescence-accelerated mouse strain P8 (SAMP8) mice were randomly divided into control and toothless groups. Removal of the upper molar teeth was performed at one month of age. Bone response was evaluated at 2, 5 and 9 months of age. Tooth loss early in life caused a significant increase in circulating corticosterone level with age. Osteoblast bone formation was suppressed and osteoclast bone resorption was activated in the toothless mice. Trabecular bone volume fraction of the vertebra and femur was decreased in the toothless mice with age. The bone quality was reduced in the toothless mice at 5 and 9 months of age, compared with the age-matched control mice. These findings indicate that tooth loss early in life impairs the dynamic homeostasis of the bone formation and bone resorption, leading to reduced bone strength with age. Long-term tooth loss may have a cumulative detrimental effect on bone health. It is important to take appropriate measures to treat tooth loss in older people for preventing and/or treating senile osteoporosis.

  8. Beneficial effects of melatonin on cardiological alterations in a murine model of accelerated aging.

    PubMed

    Forman, Katherine; Vara, Elena; García, Cruz; Kireev, Roman; Cuesta, Sara; Acuña-Castroviejo, Darío; Tresguerres, J A F

    2010-10-01

    This study investigated the effect of aging-related parameters such as inflammation, oxidative stress and cell death in the heart in an animal model of accelerated senescence and analyzed the effects of chronic administration of melatonin on these markers. Thirty male mice of senescence-accelerated prone (SAMP8) and 30 senescence-accelerated-resistant mice (SAMR1) at 2 and 10 months of age were used. Animals were divided into eight experimental groups, four from each strain: two young control groups, two old untreated control groups, and four melatonin-treated groups. Melatonin was provided at two different dosages (1 and 10 mg/kg/day) in the drinking water. After 30 days of treatment, the expression of inflammatory mediators (tumor necrosis factor-alpha, interleukin 1 and 10, NFkBp50 and NFkBp52), apoptosis markers (BAD, BAX and Bcl2) and parameters related to oxidative stress (heme oxygenases 1 and 2, endothelial and inducible nitric oxide synthases) were determined in the heart by real-time reverse transcription polymerase chain reaction (RT-PCR). Inflammation, as well as, oxidative stress and apoptosis markers was increased in old SAMP8 males, when compared to its young controls. SAMR1 mice showed significantly lower basal levels of the measured parameters and smaller increases with age or no increases at all. After treatment with melatonin, these age-altered parameters were partially reversed, especially in SAMP8 mice. The results suggest that oxidative stress and inflammation increase with aging and that chronic treatment with melatonin, a potent antioxidant, reduces these parameters. The effects were more marked in the SAMP8 animals.

  9. Elevated-temperature-induced acceleration of PACT clearing process of mouse brain tissue

    NASA Astrophysics Data System (ADS)

    Yu, Tingting; Qi, Yisong; Zhu, Jingtan; Xu, Jianyi; Gong, Hui; Luo, Qingming; Zhu, Dan

    2017-01-01

    Tissue optical clearing technique shows a great potential for neural imaging with high resolution, especially for connectomics in brain. The passive clarity technique (PACT) is a relative simple clearing method based on incubation, which has a great advantage on tissue transparency, fluorescence preservation and immunostaining compatibility for imaging tissue blocks. However, this method suffers from long processing time. Previous studies indicated that increasing temperature can speed up the clearing. In this work, we aim to systematacially and quantitatively study this influence based on PACT with graded increase of temperatures. We investigated the process of optical clearing of brain tissue block at different temperatures, and found that elevated temperature could accelerate the clearing process and also had influence on the fluorescence intensity. By balancing the advantages with drawbacks, we conclude that 42–47 °C is an alternative temperature range for PACT, which can not only produce faster clearing process, but also retain the original advantages of PACT by preserving endogenous fluorescence well, achieving fine morphology maintenance and immunostaining compatibility.

  10. Elevated-temperature-induced acceleration of PACT clearing process of mouse brain tissue

    PubMed Central

    Yu, Tingting; Qi, Yisong; Zhu, Jingtan; Xu, Jianyi; Gong, Hui; Luo, Qingming; Zhu, Dan

    2017-01-01

    Tissue optical clearing technique shows a great potential for neural imaging with high resolution, especially for connectomics in brain. The passive clarity technique (PACT) is a relative simple clearing method based on incubation, which has a great advantage on tissue transparency, fluorescence preservation and immunostaining compatibility for imaging tissue blocks. However, this method suffers from long processing time. Previous studies indicated that increasing temperature can speed up the clearing. In this work, we aim to systematacially and quantitatively study this influence based on PACT with graded increase of temperatures. We investigated the process of optical clearing of brain tissue block at different temperatures, and found that elevated temperature could accelerate the clearing process and also had influence on the fluorescence intensity. By balancing the advantages with drawbacks, we conclude that 42–47 °C is an alternative temperature range for PACT, which can not only produce faster clearing process, but also retain the original advantages of PACT by preserving endogenous fluorescence well, achieving fine morphology maintenance and immunostaining compatibility. PMID:28139694

  11. The influence of the accelerated ageing on the black screen element of the Electroink prints

    NASA Astrophysics Data System (ADS)

    Majnaric, I.; Bolanca, Z.; Bolanca Mirkovic, I.

    2010-06-01

    Printing material and prints undergo changes during ageing which can be recognized in deterioration in the physical, chemical and optical properties. The aim of this work is to determine the optical changes of the prints caused by ageing of the printing material and of the prints obtained by the application of the indirect electrophotography. The change of the screen elements in lighter halftone areas, which was obtained by the usage of the microscopic image analysis, has been discussed in the article. For the preparation of samples the following papers were used: fine art paper, recycled paper and offset paper as well as black Electroink. Three sample series were observed: prints on nonaged paper and ElectroInk, prints on aged paper and ElectroInk and prints on aged paper and nonaged ElectroInk. The investigation results show that by ageing of the uncoated printing substrates the decrease of the dots on prints can be expected, while the printing on the aged paper results in the increased reproduction of the halftone dots. The obtained results are the contribution to the explanation of the influence of the accelerated ageing process of papers which are used for printing and the aged prints on the halftone dot changes. Except the mentioned determined scientific contribution the results are applicable in the area of the printing product quality as well as in the forensic science.

  12. The relevance of aging-related changes in brain function to rehabilitation in aging-related disease

    PubMed Central

    Crosson, Bruce; McGregor, Keith M.; Nocera, Joe R.; Drucker, Jonathan H.; Tran, Stella M.; Butler, Andrew J.

    2015-01-01

    The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered. PMID:26074807

  13. The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study.

    PubMed

    Samaras, Katherine; Lutgers, Helen L; Kochan, Nicole A; Crawford, John D; Campbell, Lesley V; Wen, Wei; Slavin, Melissa J; Baune, Bernard T; Lipnicki, Darren M; Brodaty, Henry; Trollor, Julian N; Sachdev, Perminder S

    2014-04-01

    Type 2 diabetes predicts accelerated cognitive decline and brain atrophy. We hypothesized that impaired fasting glucose (IFG) and incident glucose disorders have detrimental effects on global cognition and brain volume. We further hypothesized that metabolic and inflammatory derangements accompanying hyperglycaemia contribute to change in brain structure and function. This was a longitudinal study of a community-dwelling elderly cohort with neuropsychological testing (n = 880) and brain volumes by magnetic resonance imaging (n = 312) measured at baseline and 2 years. Primary outcomes were global cognition and total brain volume. Secondary outcomes were cognitive domains (processing speed, memory, language, visuospatial and executive function) and brain volumes (hippocampal, parahippocampal, precuneus and frontal lobe). Participants were categorised as normal, impaired fasting glucose at both assessments (stable IFG), baseline diabetes or incident glucose disorders (incident diabetes or IFG at 2 years). Measures included inflammatory cytokines and oxidative metabolites. Covariates were age, sex, education, non-English speaking background, smoking, blood pressure, lipid-lowering or antihypertensive medications, mood score, apolipoprotein E genotype and baseline cognition or brain volume. Participants with incident glucose disorders had greater decline in global cognition and visuospatial function compared to normal, similar to that observed in baseline diabetes. Homocysteine was independently associated with the observed effect of diabetes on executive function. Apolipoprotein E genotype did not influence the observed effects of diabetes on cognition. Incident glucose disorders and diabetes were also associated with greater 2-year decline in total brain volume, compared to normal (40.0 ± 4.2 vs. 46.7 ± 5.7 mm(3) vs. 18.1 ± 6.2, respectively, p < 0.005). Stable IFG did not show greater decline in global cognition or brain volumes compared

  14. Accelerated long-term forgetting in aging and intra-sleep awakenings.

    PubMed

    Mary, Alison; Schreiner, Svenia; Peigneux, Philippe

    2013-01-01

    The architecture of sleep and the functional neuroanatomical networks subtending memory consolidation processes are both modified with aging, possibly leading to accelerated forgetting in long-term memory. We investigated associative learning and declarative memory consolidation processes in 16 young (18-30 years) and 16 older (65-75 years) healthy adults. Performance was tested using a cued recall procedure at the end of learning (immediate recall), and 30 min and 7 days later. A delayed recognition test was also administered on day 7. Daily sleep diaries were completed during the entire experiment. Results revealed a similar percentage of correct responses at immediate and 30-min recall in young and older participants. However, recall was significantly decreased 7 days later, with an increased forgetting in older participants. Additionally, intra-sleep awakenings were more frequent in older participants than young adults during the seven nights, and were negatively correlated with delayed recall performance on day 7 in the older group. Altogether, our results suggest a decline in verbal declarative memory consolidation processes with aging, eventually leading to accelerated long-term forgetting indicating that increased sleep fragmentation due to more frequent intra-sleep awakenings in older participants contribute to the reported age-related decline in long-term memory retrieval. Our results highlight the sensitivity of long-term forgetting measures to evidence consolidation deficits in healthy aging.

  15. Multiple Brain Markers are Linked to Age-Related Variation in Cognition.

    PubMed

    Hedden, Trey; Schultz, Aaron P; Rieckmann, Anna; Mormino, Elizabeth C; Johnson, Keith A; Sperling, Reisa A; Buckner, Randy L

    2016-04-01

    Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65-90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70-80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health.

  16. [The shrinking brain: result of normal aging or of selection bias in research?].

    PubMed

    Burgmans, S; van Boxtel, M P J

    2012-02-01

    The volume of our brain decreases as we age. This has been demonstrated by several large studies on normal aging. A recent study indicates, however, that the extent of this decline in normal aging probably has been overestimated because these studies have included subjects with preclinical disorders. In this article, an example from science is used to describe what effect selection bias may have on our model of the aging brain.

  17. Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases

    PubMed Central

    Smith, J. A.; Leonardi, T.; Huang, B.; Iraci, N.; Vega, B.; Pluchino, S.

    2015-01-01

    Multicellular organisms rely upon diverse and complex intercellular communications networks for a myriad of physiological processes. Disruption of these processes is implicated in the onset and propagation of disease and disorder, including the mechanisms of senescence at both cellular and organismal levels. In recent years, secreted extracellular vesicles (EVs) have been identified as a particularly novel vector by which cell-to-cell communications are enacted. EVs actively and specifically traffic bioactive proteins, nucleic acids, and metabolites between cells at local and systemic levels, modulating cellular responses in a bidirectional manner under both homeostatic and pathological conditions. EVs are being implicated not only in the generic aging process, but also as vehicles of pathology in a number of age-related diseases, including cancer and neurodegenerative and disease. Thus, circulating EVs—or specific EV cargoes—are being utilised as putative biomarkers of disease. On the other hand, EVs, as targeted intercellular shuttles of multipotent bioactive payloads, have demonstrated promising therapeutic properties, which can potentially be modulated and enhanced through cellular engineering. Furthermore, there is considerable interest in employing nanomedicinal approaches to mimic the putative therapeutic properties of EVs by employing synthetic analogues for targeted drug delivery. Herein we describe what is known about the origin and nature of EVs and subsequently review their putative roles in biology and medicine (including the use of synthetic EV analogues), with a particular focus on their role in aging and age-related brain diseases. PMID:24973266

  18. Cycle life estimation of lithium secondary battery by extrapolation method and accelerated aging test

    NASA Astrophysics Data System (ADS)

    Takei, K.; Kumai, K.; Kobayashi, Y.; Miyashiro, H.; Terada, N.; Iwahori, T.; Tanaka, T.

    The testing methods to estimate the life cycles of lithium ion batteries for a short period, have been developed using a commercialized cell with LiCoO 2/hard carbon cell system. The degradation reactions with increasing cycles were suggested to occur predominantly above 4 V from the results of operating voltage range divided tests. In the case of the extrapolation method using limited cycle data, the straight line approximation was useful as the cycle performance has the linearity, but the error is at most 40% in using the initial short cycle data. In the case of the accelerated aging tests using the following stress factors, the charge and/or discharge rate, large accelerated coefficients were obtained in the high charge rate and the high temperature thermal stress.

  19. Anticedants and natural prevention of environmental toxicants induced accelerated aging of skin.

    PubMed

    Tanuja Yadav; Mishra, Shivangi; Das, Shefali; Aggarwal, Shikha; Rani, Vibha

    2015-01-01

    Skin is frequently exposed to a variety of environmental and chemical agents that accelerate ageing. External stress such as UV radiations (UVR) and environmental pollutants majorly deteriorate the skin morphology, by activating certain intrinsic factors such as Reactive Oxygen Species (ROS) which trigger the activation of Matrix Metalloproteinases (MMPs) and inflammatory responses hence damaging the extracellular matrix (ECM) components. To counter this, an exogenous supply of anti-oxidants, is required since the endogenous anti-oxidant system cannot alone suffice the need. Bio-prospecting of natural resources for anti-oxidants has hence been intensified. Immense research is being carried out to identify potential plants with potent anti-oxidant activity against skin ageing. This review summarizes the major factors responsible for premature skin ageing and the plants being targeted to lessen the impact of those.

  20. Positron emission tomography and computed tomography assessments of the aging human brain

    SciTech Connect

    de Leon, M.J.; George, A.E.; Ferris, S.H.; Christman, D.R.; Fowler, J.S.; Gentes, C.I.; Brodie, J.; Reisberg, B.; Wolf, A.P.

    1984-02-01

    The relationship between alterations in brain structure and brain function was studied in vivo in both young and elderly human subjects. Computed tomography revealed significant age-related ventricular and cortical sulcal dilatation. The cortical changes were most closely related to age. Positron emission tomography failed to show regional changes in brain glucose metabolic rate. The results suggest that the normal aging brain undergoes structural atrophic changes without incurring regional metabolic changes. Examination of the correlations between the structural and the metabolic measures revealed no significant relationships. These data are discussed with respect to the significant structure-function relationships that have been reported in Alzheimer disease. 27 references, 3 figures, 2 tables.

  1. Differences between chronological and brain age are related to education and self-reported physical activity

    PubMed Central

    Steffener, Jason; Habeck, Christian; O'Shea, Deirdre; Razlighi, Qolamreza; Bherer, Louis; Stern, Yaakov

    2016-01-01

    This study investigated the relationship between education and physical activity and the difference between a physiological prediction of age and chronological age. Cortical and subcortical grey matter regional volumes were calculated from 331 healthy adults (range: 19-79 years). Multivariate analyses identified a covariance pattern of brain volumes best predicting chronological age (CA)(R2 = 47%). Individual expression of this brain pattern served as a physiologic measure of brain age (BA). The difference between CA and BA was predicted by education and self-report measures of physical activity. Education and the daily number of flights of stairs climbed were the only two significant predictors of decreased brain age. Effect sizes demonstrated that brain age decreased by 0.95 years for each year of education and by 0.58 years for one additional daily FOSC. Effects of education and FOSC on regional brain volume were largely driven by temporal and subcortical volumes. These results demonstrate that higher levels of education and daily FOSC are related to larger brain volume than predicted by chronological age which supports the utility of regional grey matter volume as a biomarker of healthy brain aging. PMID:26973113

  2. New Aging Index Using Signal Features of Both Photoplethysmograms and Acceleration Plethysmograms

    PubMed Central

    2017-01-01

    Objectives Acceleration plethysmograms (APGs) are obtained by taking the second derivative of photoplethysmograms (PPGs) and are noninvasive circulatory signals related to risk factors for atherosclerosis with age. There has been growing interest in the development of mobile devices to collect and analyze PPG single features for ambulatory health monitoring. The present study aimed to extract a new feature from the morphologies of APG and PPG signals to classify the dominant indices related to the pulsatile volume of blood in tissue according to age. Methods Ten APG and 14 PPG indices were simultaneously extracted. All indices were compared via Pearson correlation coefficients (r) and a regression analysis. We introduced a combined index extracted from both the PPG and APG indices defined as the inflection point area plus the d_peak (IPAD). The participants included 93 healthy adults aged 36–86 years with a mean ± standard deviation age of 57.43 ± 11.99 years. Results The d_peak and age index for the APG indices were significantly correlated with age (r = −0.408, p < 0.0001 and r = 0.296, p = 0.0039, respectively). Only the A1 time for PPG indices was moderately correlated with age (r = −0.247, p = 0.017). The stiffness index, including individual height information, was not related to age (r = −0.031, p = 0.7713). However, the combined IPAD index was significantly more correlated with age (r = 0.56, p < 0.001) than the other indices. Conclusions The proposed index outperformed the other 24 indices for evaluating vascular aging. We suggest that the IPAD is a significant factor related to the clinical information embedded in the PPG waveform. PMID:28261531

  3. Acceleration of Age-Associated Methylation Patterns in HIV-1-Infected Adults

    PubMed Central

    Sehl, Mary; Sinsheimer, Janet S.; Hultin, Patricia M.; Hultin, Lance E.; Quach, Austin; Martínez-Maza, Otoniel; Horvath, Steve; Vilain, Eric; Jamieson, Beth D.

    2015-01-01

    Patients with treated HIV-1-infection experience earlier occurrence of aging-associated diseases, raising speculation that HIV-1-infection, or antiretroviral treatment, may accelerate aging. We recently described an age-related co-methylation module comprised of hundreds of CpGs; however, it is unknown whether aging and HIV-1-infection exert negative health effects through similar, or disparate, mechanisms. We investigated whether HIV-1-infection would induce age-associated methylation changes. We evaluated DNA methylation levels at >450,000 CpG sites in peripheral blood mononuclear cells (PBMC) of young (20-35) and older (36-56) adults in two separate groups of participants. Each age group for each data set consisted of 12 HIV-1-infected and 12 age-matched HIV-1-uninfected samples for a total of 96 samples. The effects of age and HIV-1 infection on methylation at each CpG revealed a strong correlation of 0.49, p<1 x10-200 and 0.47, p<1x10-200. Weighted gene correlation network analysis (WGCNA) identified 17 co-methylation modules; module 3 (ME3) was significantly correlated with age (cor=0.70) and HIV-1 status (cor=0.31). Older HIV-1+ individuals had a greater number of hypermethylated CpGs across ME3 (p=0.015). In a multivariate model, ME3 was significantly associated with age and HIV status (Data set 1: βage= 0.007088, p=2.08 x 10-9; βHIV= 0.099574, p=0.0011; Data set 2: βage= 0.008762, p=1.27x 10-5; βHIV= 0.128649, p= 0.0001). Using this model, we estimate that HIV-1 infection accelerates age-related methylation by approximately 13.7 years in data set 1 and 14.7 years in data set 2. The genes related to CpGs in ME3 are enriched for polycomb group target genes known to be involved in cell renewal and aging. The overlap between ME3 and an aging methylation module found in solid tissues is also highly significant (Fisher-exact p=5.6 x 10-6, odds ratio=1.91). These data demonstrate that HIV-1 infection is associated with methylation patterns that are similar to

  4. Gender and iron genes may modify associations between brain iron and memory in healthy aging.

    PubMed

    Bartzokis, George; Lu, Po H; Tingus, Kathleen; Peters, Douglas G; Amar, Chetan P; Tishler, Todd A; Finn, J Paul; Villablanca, Pablo; Altshuler, Lori L; Mintz, Jim; Neely, Elizabeth; Connor, James R

    2011-06-01

    Brain iron increases with age and is abnormally elevated early in the disease process in several neurodegenerative disorders that impact memory including Alzheimer's disease (AD). Higher brain iron levels are associated with male gender and presence of highly prevalent allelic variants in genes encoding for iron metabolism proteins (hemochromatosis H63D (HFE H63D) and transferrin C2 (TfC2)). In this study, we examined whether in healthy older individuals memory performance is associated with increased brain iron, and whether gender and gene variant carrier (IRON+) vs noncarrier (IRON-) status (for HFE H63D/TfC2) modify the associations. Tissue iron deposited in ferritin molecules can be measured in vivo with magnetic resonance imaging utilizing the field-dependent relaxation rate increase (FDRI) method. FDRI was assessed in hippocampus, basal ganglia, and white matter, and IRON+ vs IRON- status was determined in a cohort of 63 healthy older individuals. Three cognitive domains were assessed: verbal memory (delayed recall), working memory/attention, and processing speed. Independent of gene status, worse verbal-memory performance was associated with higher hippocampal iron in men (r=-0.50, p=0.003) but not in women. Independent of gender, worse verbal working memory performance was associated with higher basal ganglia iron in IRON- group (r=-0.49, p=0.005) but not in the IRON+ group. Between-group interactions (p=0.006) were noted for both of these associations. No significant associations with white matter or processing speed were observed. The results suggest that in specific subgroups of healthy older individuals, higher accumulations of iron in vulnerable gray matter regions may adversely impact memory functions and could represent a risk factor for accelerated cognitive decline. Combining genetic and MRI biomarkers may provide opportunities to design primary prevention clinical trials that target high-risk groups.

  5. Priming of microglia in a DNA-repair deficient model of accelerated aging.

    PubMed

    Raj, Divya D A; Jaarsma, Dick; Holtman, Inge R; Olah, Marta; Ferreira, Filipa M; Schaafsma, Wandert; Brouwer, Nieske; Meijer, Michel M; de Waard, Monique C; van der Pluijm, Ingrid; Brandt, Renata; Kreft, Karim L; Laman, Jon D; de Haan, Gerald; Biber, Knut P H; Hoeijmakers, Jan H J; Eggen, Bart J L; Boddeke, Hendrikus W G M

    2014-09-01

    Aging is associated with reduced function, degenerative changes, and increased neuroinflammation of the central nervous system (CNS). Increasing evidence suggests that changes in microglia cells contribute to the age-related deterioration of the CNS. The most prominent age-related change of microglia is enhanced sensitivity to inflammatory stimuli, referred to as priming. It is unclear if priming is due to intrinsic microglia ageing or induced by the ageing neural environment. We have studied this in Ercc1 mutant mice, a DNA repair-deficient mouse model that displays features of accelerated aging in multiple tissues including the CNS. In Ercc1 mutant mice, microglia showed hallmark features of priming such as an exaggerated response to peripheral lipopolysaccharide exposure in terms of cytokine expression and phagocytosis. Specific targeting of the Ercc1 deletion to forebrain neurons resulted in a progressive priming response in microglia exemplified by phenotypic alterations. Summarizing, these data show that neuronal genotoxic stress is sufficient to switch microglia from a resting to a primed state.

  6. Histone modifications change with age, dietary restriction and rapamycin treatment in mouse brain

    PubMed Central

    Gong, Huan; Qian, Hong; Ertl, Robin; Astle, Clinton M.; Wang, Gang G.; Harrison, David E.; Xu, Xiangru

    2015-01-01

    The risk of developing neurodegenerative disorders such as Alzheimer's disease (AD) increases dramatically with age. Understanding the underlying mechanisms of brain aging is crucial for developing preventative and/or therapeutic approaches for age-associated neurological diseases. Recently, it has been suggested that epigenetic factors, such as histone modifications, maybe be involved in brain aging and age-related neurodegenerations. In this study, we investigated 14 histone modifications in brains of a cohort of young (3 months), old (22 months), and old age-matched dietary restricted (DR) and rapamycin treated BALB/c mice. Results showed that 7 out of all measured histone markers were changed drastically with age. Intriguingly, histone methylations in brain tissues, including H3K27me3, H3R2me2, H3K79me3 and H4K20me2 tend to disappear with age but can be partially restored by both DR and rapamycin treatment. However, both DR and rapamycin treatment also have a significant impact on several other histone modifications such as H3K27ac, H4K16ac, H4R3me2, and H3K56ac, which do not change as animal ages. This study provides the first evidence that a broad spectrum of histone modifications may be involved in brain aging. Besides, this study suggests that both DR and rapamycin may slow aging process in mouse brain via these underlying epigenetic mechanisms. PMID:26021816

  7. Mitochondrial dysfunction in rat brain with aging Involvement of complex I, reactive oxygen species and cardiolipin.

    PubMed

    Petrosillo, G; Matera, M; Casanova, G; Ruggiero, F M; Paradies, G

    2008-11-01

    Reactive oxygen species (ROS) are considered a key factor in brain aging process. Mitochondrial respiration is an important site of ROS production and hence a potential contributor to brain functional changes with aging. In this study we examined the effect of aging on complex I activity, oxygen consumption, ROS production and phospholipid composition in rat brain mitochondria. The activity of complex I was reduced by 30% in brain mitochondria from 24 months aged rats relative to young animals. These changes in complex I activity were associated with parallel changes in state 3 respiration. H(2)O(2) generation was significantly increased in mitochondria isolated from aged rats. The mitochondrial content of cardiolipin, a phospholipid required for optimal activity of complex I, decreased by 31% as function of aging, while there was a significant increase in the level of peroxidized cardiolipin. The age-related decrease in complex I activity in brain mitochondria could be reversed by exogenously added cardiolipin. This effect of cardiolipin could not be replaced by other phospholipids. It is proposed that aging causes brain mitochondrial complex I dysfunction which can be attributed to ROS-induced cardiolipin oxidation. These findings may prove useful in elucidating the mechanism underlying mitochondrial dysfunction associated with brain aging.

  8. Brain Na+, K+-ATPase Activity In Aging and Disease

    PubMed Central

    de Lores Arnaiz, Georgina Rodríguez; Ordieres, María Graciela López

    2014-01-01

    , enzyme changes in diverse neurological diseases as well as during aging, have been summarized. Issues refer mainly to Na+, K+-ATPase studies in ischemia, brain injury, depression and mood disorders, mania, stress, Alzheimer´s disease, learning and memory, and neuronal hyperexcitability and epilepsy. PMID:25018677

  9. Metabolomics of human brain aging and age-related neurodegenerative diseases.

    PubMed

    Jové, Mariona; Portero-Otín, Manuel; Naudí, Alba; Ferrer, Isidre; Pamplona, Reinald

    2014-07-01

    Neurons in the mature human central nervous system (CNS) perform a wide range of motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse functional output requires a great diversity of CNS neuronal and non-neuronal populations. Metabolomics encompasses the study of the complete set of metabolites/low-molecular-weight intermediates (metabolome), which are context-dependent and vary according to the physiology, developmental state, or pathologic state of the cell, tissue, organ, or organism. Therefore, the use of metabolomics can help to unravel the diversity-and to disclose the specificity-of metabolic traits and their alterations in the brain and in fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of aging and neurodegenerative diseases. Here, we review the current applications of metabolomics in studies of CNS aging and certain age-related neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Neurometabolomics will increase knowledge of the physiologic and pathologic functions of neural cells and will place the concept of selective neuronal vulnerability in a metabolic context.

  10. Age-dependent changes in task-based modular organization of the human brain.

    PubMed

    Schlesinger, Kimberly J; Turner, Benjamin O; Lopez, Brian A; Miller, Michael B; Carlson, Jean M

    2017-02-01

    As humans age, cognition and behavior change significantly, along with associated brain function and organization. Aging has been shown to decrease variability in functional magnetic resonance imaging (fMRI) signals, and to affect the modular organization of human brain function. In this work, we use complex network analysis to investigate the dynamic community structure of large-scale brain function, asking how evolving communities interact with known brain systems, and how the dynamics of communities and brain systems are affected by age. We analyze dynamic networks derived from fMRI scans of 104 human subjects performing a word memory task, and determine the time-evolving modular structure of these networks by maximizing the multislice modularity, thereby identifying distinct communities, or sets of brain regions with strong intra-set functional coherence. To understand how community structure changes over time, we examine the number of communities as well as the flexibility, or the likelihood that brain regions will switch between communities. We find a significant positive correlation between age and both these measures: younger subjects tend to have less fragmented and more coherent communities, and their brain regions tend to change communities less often during the memory task. We characterize the relationship of community structure to known brain systems by the recruitment coefficient, or the probability of a brain region being grouped in the same community as other regions in the same system. We find that regions associated with cingulo-opercular, somatosensory, ventral attention, and subcortical circuits have a significantly higher recruitment coefficient in younger subjects. This indicates that the within-system functional coherence of these specific systems during the memory task declines with age. Such a correspondence does not exist for other systems (e.g. visual and default mode), whose recruitment coefficients remain relatively uniform across ages

  11. Effect of accelerated environmental aging on tensile properties of oil palm/jute hybrid composites

    NASA Astrophysics Data System (ADS)

    Jawaid, M.; Saba, N.; Alothman, O.; Paridah, M. T.

    2016-11-01

    Recently natural fibre based hybrid composites are receiving growing consideration due to environmental and biodegradability properties. In order to look behaviour of hybrid composites in outdoor applications, its environmental degradation properties such as UV accelerated weathering properties need to analyze. In this study oil palm empty fruit bunch (EFB) and jute fibres reinforced hybrid composites, pure EFB, pure jute and epoxy composites were fabricated through hand lay-up techniques. Hybrid composites with different layering pattern (EFB/jute/EFB and Jute/EFB/jute) while maintaining 40 wt. % total fibre loading were fabricates to compared with EFB and jute composites. Effect of UV accelerated environmental aging on tensile properties of epoxy, pure EFB, pure jute, and hybrid composites were assessed and evaluate under UV exposure. Tensile samples of all composites were subjected to accelerated weathering for 100h, at temperature (75°C), relative humidity (35%), Light (125 W/m2), and water spray off. Obtained results indicated that there is reduction in tensile strength, modulus and elongation at break values of hybrid and pure composites due to degradation of lignin and fibre-matrix interfacial bonding.

  12. Holocene age of the Yuha burial: Direct radiocarbon determinations by accelerator mass spectrometry

    USGS Publications Warehouse

    Stafford, Thomas W.; Jull, A.J.T.; Zabel, T.H.; Donahue, D.J.; Duhamel, R.C.; Brendel, K.; Haynes, C.V.; Bischoff, J.L.; Payen, L.A.; Taylor, R.E.

    1984-01-01

    The view that human populations may not have arrived in the Western Hemisphere before about 12,000 radiocarbon yr BP1,2 has been challenged by claims of much greater antiquity for a small number of archaeological sites and human skeleton samples. One such site is the Homo sapiens sapiens cairn burial excavated in 1971 from the Yuha desert, Imperial County, California3-5. Radiocarbon analysis of caliche coating one of the bones of the skeleton yielded a radiocarbon age of 21,500??1,000 yr BP4, while radiocarbon and uranium series analyses of caliche coating a cairn boulder yielded ages of 22,125??400 and 19,000??3,000 yr BP, respectively5. The late Pleistocene age assignment to the Yuha burial has been challenged by comparing the cultural context of the burial with other cairn burials in the same region6, on the basis of the site's geomorphological context and from radiocarbon analyses of soil caliches. 7,8 In rebuttal, arguments in defence of the original age assignment have been presented9,10 as well as an amino acid racemization analysis on the Yuha skeleton indicating an age of 23,600??2,600 yr BP11. The tandem accelerator mass spectrometer at the University of Arizona has now been used to measure the ratio of 14C/13C in several organic and inorganic fractions of post-cranial bone from the Yuha H. sapiens sapiens skeleton. Isotope ratios from six chemical fractions all yielded radiocarbon ages for the skeleton of less than 4,000 yr BP. These results indicate that the Yuha skeleton is of Holocene age, in agreement with the cultural context of the burial, and in disagreement with the previously assigned Pleistocene age of 19,000-23,000 yr. ?? 1984 Nature Publishing Group.

  13. HRT and its effect on normal ageing of the brain and dementia

    PubMed Central

    Compton, Jacqueline; van Amelsvoort, Therese; Murphy, Declan

    2001-01-01

    There are significant gender differences in human brain disease. For example, females are significantly more likely to suffer from Alzheimer's disease (AD) than men (even after correcting for differences in life expectancy), and females on hormone replacement therapy (HRT) are significantly less likely to suffer from Alzheimer's disease than women who do not take HRT. However the neurobiological basis to these differences in clinical brain disease were unknown until relatively recently. In this review we will discuss results of studies that show; (i) gender differences in human brain disease are most likely to be explained by gender differences in brain development and ageing; (ii) sex steroids have a significant effect on the brain; (iii) sex steroids are crucial to the development and ageing of brain regions affected in age-related brain diseases (for example AD); (iv) sex steroids interact with neuronal networks and chemical systems at many different levels; (v) sex steroids affect cognitive function in elderly women. Thus, the current literature supports the hypothesis that sex steroids can modulate brain ageing, and this provides a neurobiological explanation for the significantly higher prevalence of AD in females who do not take HRT, and may lead to new treatment approaches for age-related brain disease including AD. PMID:11736875

  14. Accelerated failure time models provide a useful statistical framework for aging research.

    PubMed

    Swindell, William R

    2009-03-01

    Survivorship experiments play a central role in aging research and are performed to evaluate whether interventions alter the rate of aging and increase lifespan. The accelerated failure time (AFT) model is seldom used to analyze survivorship data, but offers a potentially useful statistical approach that is based upon the survival curve rather than the hazard function. In this study, AFT models were used to analyze data from 16 survivorship experiments that evaluated the effects of one or more genetic manipulations on mouse lifespan. Most genetic manipulations were found to have a multiplicative effect on survivorship that is independent of age and well-characterized by the AFT model "deceleration factor". AFT model deceleration factors also provided a more intuitive measure of treatment effect than the hazard ratio, and were robust to departures from modeling assumptions. Age-dependent treatment effects, when present, were investigated using quantile regression modeling. These results provide an informative and quantitative summary of survivorship data associated with currently known long-lived mouse models. In addition, from the standpoint of aging research, these statistical approaches have appealing properties and provide valuable tools for the analysis of survivorship data.

  15. The signaling pathways by which the Fas/FasL system accelerates oocyte aging.

    PubMed

    Zhu, Jiang; Lin, Fei-Hu; Zhang, Jie; Lin, Juan; Li, Hong; Li, You-Wei; Tan, Xiu-Wen; Tan, Jing-He

    2016-02-01

    In spite of great efforts, the mechanisms for postovulatory oocyte aging are not fully understood. Although our previous work showed that the FasL/Fas signaling facilitated oocyte aging, the intra-oocyte signaling pathways are unknown. Furthermore, the mechanisms by which oxidative stress facilitates oocyte aging and the causal relationship between Ca2+ rises and caspase-3 activation and between the cell cycle and apoptosis during oocyte aging need detailed investigations. Our aim was to address these issues by studying the intra-oocyte signaling pathways for Fas/FasL to accelerate oocyte aging. The results indicated that sFasL released by cumulus cells activated Fas on the oocyte by increasing reactive oxygen species via activating NADPH oxidase. The activated Fas triggered Ca2+ release from the endoplasmic reticulum by activating phospholipase C-γ pathway and cytochrome c pathway. The cytoplasmic Ca2+ rises activated calcium/calmodulin-dependent protein kinase II (CaMKII) and caspase-3. While activated CaMKII increased oocyte susceptibility to activation by inactivating maturation-promoting factor (MPF) through cyclin B degradation, the activated caspase-3 facilitated further Ca2+releasing that activates more caspase-3 leading to oocyte fragmentation. Furthermore, caspase-3 activation and fragmentation were prevented in oocytes with a high MPF activity, suggesting that an oocyte must be in interphase to undergo apoptosis.

  16. Brain amyloid-β oligomers in ageing and Alzheimer's disease.

    PubMed

    Lesné, Sylvain E; Sherman, Mathew A; Grant, Marianne; Kuskowski, Michael; Schneider, Julie A; Bennett, David A; Ashe, Karen H

    2013-05-01

    Alzheimer's disease begins about two decades before the onset of symptoms or neuron death, and is believed to be caused by pathogenic amyloid-β aggregates that initiate a cascade of molecular events culminating in widespread neurodegeneration. The microtubule binding protein tau may mediate the effects of amyloid-β in this cascade. Amyloid plaques comprised of insoluble, fibrillar amyloid-β aggregates are the most characteristic feature of Alzheimer's disease. However, the correspondence between the distribution of plaques and the pattern of neurodegeneration is tenuous. This discrepancy has stimulated the investigation of other amyloid-β aggregates, including soluble amyloid-β oligomers. Different soluble amyloid-β oligomers have been studied in several mouse models, but not systematically in humans. Here, we measured three amyloid-β oligomers previously described in mouse models-amyloid-β trimers, Aβ*56 and amyloid-β dimers-in brain tissue from 75 cognitively intact individuals, ranging from young children to the elderly, and 58 impaired subjects with mild cognitive impairment or probable Alzheimer's disease. As in mouse models, where amyloid-β trimers appear to be the fundamental amyloid-β assembly unit of Aβ*56 and are present in young mice prior to memory decline, amyloid-β trimers in humans were present in children and adolescents; their levels rose gradually with age and were significantly above baseline in subjects in their 70s. Aβ*56 levels were negligible in children and young adults, rose significantly above baseline in subjects in their 40s and increased steadily thereafter. Amyloid-β dimers were undetectable until subjects were in their 60s; their levels then increased sharply and correlated with plaque load. Remarkably, in cognitively intact individuals we found strong positive correlations between Aβ*56 and two pathological forms of soluble tau (tau-CP13 and tau-Alz50), and negative correlations between Aβ*56 and two postsynaptic

  17. The electrical performance of polymeric insulating materials under accelerated aging in a fog chamber

    SciTech Connect

    Gorur, R.S.; Cherney, E.A.; Hackam, R. ); Orbeck, T. )

    1988-07-01

    A comparative study of the ac (60 Hz) surface aging in a fog chamber is reported on cylindrical rod samples of high temperature vulcanized (HTV) silicone rubber and ethylene propylene diene monomer (EPDM) rubber containing various amounts of alumina trihydrate (ATH) and/or silica fillers. In low conductivity (250 ..mu..S/cm) fog, silicone rubber performed better than EPDM samples whereas in high conductivity (1000 ..mu..S/cm) fog, the order of performance was reversed. The mechanisms by which fillers impart tracking and erosion resistance to materials is discussed as influenced by the experimental conditions of the accelerated aging tests. Surface studies by ESCA (Electron Spectroscopy for Chemical Analysis) demonstrate that the hydrophobicity of silicone rubber, despite the accumulation of surface contamination, can be attributed to migration of low molecular weight polymer chains and/or mobile fluids, such as silicone oil.

  18. Expression of fatty acid binding proteins is altered in aged mouse brain.

    PubMed

    Pu, L; Igbavboa, U; Wood, W G; Roths, J B; Kier, A B; Spener, F; Schroeder, F

    1999-08-01

    Brain membrane lipid fatty acid composition and consequently membrane fluidity change with increasing age. Intracellular fatty acid binding proteins (FABPs) such as heart H-FABP and the brain specific B-FABP, detected by immunoblotting of brain tissue, are thought to be involved in fatty acid uptake, metabolism, and differentiation in brain. Yet, almost nothing is known regarding the effect of age on the expression of the cytosolic fatty acid binding proteins (FABPs) or their content in brain subfractions. Electrophoresis and quantitative immunoblotting were used to examine the content of these FABPs in synaptosomes in brains from 4, 15, and 25 month old C57BL/6NNia male mice. Brain H-FABP and B-FABP were differentially expressed in mouse brain subcellular fractions. Brain H-FABP was highly concentrated in synaptosomal cytosol. The level of brain H-FABP in synaptosomes, synaptosomal cytosol, and intrasynaptosomal membranes was decreased 33, 35, and 43%, respectively, in 25 month old mice. B-FABP was detected in lower quantity than H-FABP. More important, B-FABP decreased in synaptosomes, synaptic plasma membranes, and synaptosomal cytosol from brains of 25 month old mice. In contrast to H-FABP, B-FABP was not detectable in the intrasynaptosomal membranes in any of the three age groups of mice. In conclusion, expression of both H-FABP and B-FABP was markedly reduced in aged mouse brain. Age differences in brain H-FABP and B-FABP levels in synaptosomal plasma membranes and synaptosomal cytosol may be important factors modulating neuronal differentiation and function.

  19. Age- and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats

    EPA Pesticide Factsheets

    Differences in various mitochondrial bioenergetics parameters in different brain regions in different age groups.This dataset is associated with the following publication:Pandya, J.D., J. Royland , R.C. McPhail, P.G. Sullivan, and P. Kodavanti. Age-and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats. NEUROBIOLOGY OF AGING. Elsevier Science Ltd, New York, NY, USA, 42: 25-34, (2016).

  20. Behavioral Outcomes Differ between Rotational Acceleration and Blast Mechanisms of Mild Traumatic Brain Injury

    PubMed Central

    Stemper, Brian D.; Shah, Alok S.; Budde, Matthew D.; Olsen, Christopher M.; Glavaski-Joksimovic, Aleksandra; Kurpad, Shekar N.; McCrea, Michael; Pintar, Frank A.

    2016-01-01

    Mild traumatic brain injury (mTBI) can result from a number of mechanisms, including blunt impact, head rotational acceleration, exposure to blast, and penetration of projectiles. Mechanism is likely to influence the type, severity, and chronicity of outcomes. The objective of this study was to determine differences in the severity and time course of behavioral outcomes following blast and rotational mTBI. The Medical College of Wisconsin (MCW) Rotational Injury model and a shock tube model of primary blast injury were used to induce mTBI in rats and behavioral assessments were conducted within the first week, as well as 30 and 60 days following injury. Acute recovery time demonstrated similar increases over protocol-matched shams, indicating acute injury severity equivalence between the two mechanisms. Post-injury behavior in the elevated plus maze demonstrated differing trends, with rotationally injured rats acutely demonstrating greater activity, whereas blast-injured rats had decreased activity that developed at chronic time points. Similarly, blast-injured rats demonstrated trends associated with cognitive deficits that were not apparent following rotational injuries. These findings demonstrate that rotational and blast injury result in behavioral changes with different qualitative and temporal manifestations. Whereas rotational injury was characterized by a rapidly emerging phenotype consistent with behavioral disinhibition, blast injury was associated with emotional and cognitive differences that were not evident acutely, but developed later, with an anxiety-like phenotype still present in injured animals at our most chronic measurements. PMID:27014184

  1. Behavioral Outcomes Differ between Rotational Acceleration and Blast Mechanisms of Mild Traumatic Brain Injury.

    PubMed

    Stemper, Brian D; Shah, Alok S; Budde, Matthew D; Olsen, Christopher M; Glavaski-Joksimovic, Aleksandra; Kurpad, Shekar N; McCrea, Michael; Pintar, Frank A

    2016-01-01

    Mild traumatic brain injury (mTBI) can result from a number of mechanisms, including blunt impact, head rotational acceleration, exposure to blast, and penetration of projectiles. Mechanism is likely to influence the type, severity, and chronicity of outcomes. The objective of this study was to determine differences in the severity and time course of behavioral outcomes following blast and rotational mTBI. The Medical College of Wisconsin (MCW) Rotational Injury model and a shock tube model of primary blast injury were used to induce mTBI in rats and behavioral assessments were conducted within the first week, as well as 30 and 60 days following injury. Acute recovery time demonstrated similar increases over protocol-matched shams, indicating acute injury severity equivalence between the two mechanisms. Post-injury behavior in the elevated plus maze demonstrated differing trends, with rotationally injured rats acutely demonstrating greater activity, whereas blast-injured rats had decreased activity that developed at chronic time points. Similarly, blast-injured rats demonstrated trends associated with cognitive deficits that were not apparent following rotational injuries. These findings demonstrate that rotational and blast injury result in behavioral changes with different qualitative and temporal manifestations. Whereas rotational injury was characterized by a rapidly emerging phenotype consistent with behavioral disinhibition, blast injury was associated with emotional and cognitive differences that were not evident acutely, but developed later, with an anxiety-like phenotype still present in injured animals at our most chronic measurements.

  2. CUDA-based acceleration of collateral filtering in brain MR images

    NASA Astrophysics Data System (ADS)

    Li, Cheng-Yuan; Chang, Herng-Hua

    2017-02-01

    Image denoising is one of the fundamental and essential tasks within image processing. In medical imaging, finding an effective algorithm that can remove random noise in MR images is important. This paper proposes an effective noise reduction method for brain magnetic resonance (MR) images. Our approach is based on the collateral filter which is a more powerful method than the bilateral filter in many cases. However, the computation of the collateral filter algorithm is quite time-consuming. To solve this problem, we improved the collateral filter algorithm with parallel computing using GPU. We adopted CUDA, an application programming interface for GPU by NVIDIA, to accelerate the computation. Our experimental evaluation on an Intel Xeon CPU E5-2620 v3 2.40GHz with a NVIDIA Tesla K40c GPU indicated that the proposed implementation runs dramatically faster than the traditional collateral filter. We believe that the proposed framework has established a general blueprint for achieving fast and robust filtering in a wide variety of medical image denoising applications.

  3. Diet restriction delays accelerated aging and genomic stress in DNA repair deficient mice

    PubMed Central

    Vermeij, W.P.; Dollé, M.E.T.; Reiling, E.; Jaarsma, D.; Payan-Gomez, C.; Bombardieri, C.R.; Wu, H.; Roks, A.J.M.; Botter, S.M.; van der Eerden, B.C.; Youssef, S.A.; Kuiper, R.V.; Nagarajah, B.; van Oostrom, C.T.; Brandt, R.M.C.; Barnhoorn, S.; Imholz, S.; Pennings, J.L.A.; de Bruin, A.; Gyenis, Á.; Pothof, J.; Vijg, J.; van Steeg, H.; Hoeijmakers, J.H.J.

    2016-01-01

    DNA repair-deficient Ercc1Δ/− mice show numerous accelerated aging features limiting lifespan to 4–6 month1–4. Simultaneously they exhibit a ‘survival response’, which suppresses growth and enhances maintenance, resembling the anti-aging response induced by dietary restriction (DR)1,5. Here we report that subjecting these progeroid, dwarf mutants to 30% DR tripled median and maximal remaining lifespan, and drastically retarded numerous aspects of accelerated aging, e.g. DR animals retained 50% more neurons and maintained full motoric function, even far beyond the lifespan of ad libitum (AL) animals. Repair-deficient, progeroid Xpg−/− mice, a Cockayne syndrome model6, responded similarly, extending this observation to other repair mutants. The DR response in Ercc1Δ/− mice closely resembled DR in wild type animals. Interestingly, AL Ercc1Δ/− liver showed preferential extinction of expression of long genes, a phenomenon we also observe in several normal aging tissues. This is consistent with accumulation of stochastic, transcription-blocking lesions, affecting long genes more than short ones. DR largely prevented declining transcriptional output and reduced γH2AX DNA damage foci, indicating that DR preserves genome function by alleviating DNA damage. Our findings establish Ercc1Δ/− mice as powerful model for interventions sustaining health, reveal untapped potential for reducing endogenous damage, provide new venues for understanding the molecular mechanism of DR, and suggest a counterintuitive DR-like therapy for human progeroid genome instability syndromes and possibly neurodegeneration in general. PMID:27556946

  4. Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice.

    PubMed

    Vermeij, W P; Dollé, M E T; Reiling, E; Jaarsma, D; Payan-Gomez, C; Bombardieri, C R; Wu, H; Roks, A J M; Botter, S M; van der Eerden, B C; Youssef, S A; Kuiper, R V; Nagarajah, B; van Oostrom, C T; Brandt, R M C; Barnhoorn, S; Imholz, S; Pennings, J L A; de Bruin, A; Gyenis, Á; Pothof, J; Vijg, J; van Steeg, H; Hoeijmakers, J H J

    2016-09-15

    Mice deficient in the DNA excision-repair gene Ercc1 (Ercc1(∆/-)) show numerous accelerated ageing features that limit their lifespan to 4-6 months. They also exhibit a 'survival response', which suppresses growth and enhances cellular maintenance. Such a response resembles the anti-ageing response induced by dietary restriction (also known as caloric restriction). Here we report that a dietary restriction of 30% tripled the median and maximal remaining lifespans of these progeroid mice, strongly retarding numerous aspects of accelerated ageing. Mice undergoing dietary restriction retained 50% more neurons and maintained full motor function far beyond the lifespan of mice fed ad libitum. Other DNA-repair-deficient, progeroid Xpg(-/-) (also known as Ercc5(-/-)) mice, a model of Cockayne syndrome, responded similarly. The dietary restriction response in Ercc1(∆/-) mice closely resembled the effects of dietary restriction in wild-type animals. Notably, liver tissue from Ercc1(∆/-) mice fed ad libitum showed preferential extinction of the expression of long genes, a phenomenon we also observed in several tissues ageing normally. This is consistent with the accumulation of stochastic, transcription-blocking lesions that affect long genes more than short ones. Dietary restriction largely prevented this declining transcriptional output and reduced the number of γH2AX DNA damage foci, indicating that dietary restriction preserves genome function by alleviating DNA damage. Our findings establish the Ercc1(∆/-) mouse as a powerful model organism for health-sustaining interventions, reveal potential for reducing endogenous DNA damage, facilitate a better understanding of the molecular mechanism of dietary restriction and suggest a role for counterintuitive dietary-restriction-like therapy for human progeroid genome instability syndromes and possibly neurodegeneration in general.

  5. A Model-based Prognostics Methodology for Electrolytic Capacitors Based on Electrical Overstress Accelerated Aging

    NASA Technical Reports Server (NTRS)

    Celaya, Jose; Kulkarni, Chetan; Biswas, Gautam; Saha, Sankalita; Goebel, Kai

    2011-01-01

    A remaining useful life prediction methodology for electrolytic capacitors is presented. This methodology is based on the Kalman filter framework and an empirical degradation model. Electrolytic capacitors are used in several applications ranging from power supplies on critical avionics equipment to power drivers for electro-mechanical actuators. These devices are known for their comparatively low reliability and given their criticality in electronics subsystems they are a good candidate for component level prognostics and health management. Prognostics provides a way to assess remaining useful life of a capacitor based on its current state of health and its anticipated future usage and operational conditions. We present here also, experimental results of an accelerated aging test under electrical stresses. The data obtained in this test form the basis for a remaining life prediction algorithm where a model of the degradation process is suggested. This preliminary remaining life prediction algorithm serves as a demonstration of how prognostics methodologies could be used for electrolytic capacitors. In addition, the use degradation progression data from accelerated aging, provides an avenue for validation of applications of the Kalman filter based prognostics methods typically used for remaining useful life predictions in other applications.

  6. Macrophage Response to UHMWPE Submitted to Accelerated Ageing in Hydrogen Peroxide.

    PubMed

    Rocha, Magda F G; Mansur, Alexandra A P; Martins, Camila P S; Barbosa-Stancioli, Edel F; Mansur, Herman S

    2010-06-10

    Ultra-high molecular weight polyethylene (UHMWPE) has been the most commonly used bearing material in total joint arthroplasty. Wear and oxidation fatigue resistance of UHMWPE are regarded as two important properties to extend the longevity of knee prostheses. The present study investigated the accelerated ageing of UHMWPE in hydrogen peroxide highly oxidative chemical environment. The sliced samples of UHMWPE were oxidized in a hydrogen peroxide solution for 120 days with their total level of oxidation (Iox) characterized by Fourier Transformed Infrared Spectroscopy (FTIR). The potential inflammatory response, cell viability and biocompatibility of such oxidized UHMWPE systems were assessed by a novel biological in vitro assay based on the secretion of nitric oxide (NO) by activated murine macrophages with gamma interferon (IFN-gamma) cytokine and lipopolysaccharide (LPS). Furthermore, macrophage morphologies in contact with UHMWPE oxidized surfaces were analyzed by cell spreading-adhesion procedure using scanning electron microscopy (SEM). The results have given significant evidence that the longer the period of accelerated aging of UHMWPE the higher was the macrophage inflammatory equivalent response based on NO secretion analysis.

  7. Validation of accelerated ageing of Thales rotary Stirling cryocoolers for the estimation of MTTF

    NASA Astrophysics Data System (ADS)

    Seguineau, C.,; Cauquil, J.-M.; Martin, J.-Y.; Benschop, T.

    2016-05-01

    The cooled IR detectors are used in a wide range of applications. Most of the time, the cryocoolers are one of the components dimensioning the lifetime of the system. The current market needs tend to reliability figures higher than 15,000hrs in "standard conditions". Field returns are hardly useable mostly because of the uncertain environmental conditions of use, or the differences in user profiles. A previous paper explains how Thales Cryogenics has developed an approach based on accelerated ageing and statistical analysis [1]. The aim of the current paper is to compare results obtained on accelerated ageing on one side, and on the other side, specific field returns where the conditions of use are well known. The comparison between prediction and effective failure rate is discussed. Moreover, a specific focus is done on how some new applications of cryocoolers (continuous operation at a specific temperature) can increase the MTTF. Some assumptions are also exposed on how the failure modes, effects and criticality analysis evolves for continuous operation at a specific temperature and compared to experimental data.

  8. Bisphenol A exposure accelerated the aging process in the nematode Caenorhabditis elegans.

    PubMed

    Tan, Ling; Wang, Shunchang; Wang, Yun; He, Mei; Liu, Dahai

    2015-06-01

    Bisphenol A (BPA) is a well-known environmental estrogenic disruptor that causes adverse effects. Recent studies have found that chronic exposure to BPA is associated with a high incidence of several age-related diseases. Aging is characterized by progressive function decline, which affects quality of life. However, the effects of BPA on the aging process are largely unknown. In the present study, by using the nematode Caenorhabditis elegans as a model, we investigated the influence of BPA exposure on the aging process. The decrease in body length, fecundity, and population size and the increased egg laying defection suggested that BPA exposure resulted in fitness loss and reproduction aging in this animal. Lifetime exposure of worms to BPA shortened the lifespan in a dose-dependant manner. Moreover, prolonged BPA exposure resulted in age-related behavior degeneration and the accumulation of lipofuscin and lipid peroxide products. The expression of mitochondria-specific HSP-6 and endoplasmic reticulum (ER)-related HSP-70 exhibited hormetic decrease. The expression of ER-related HSP-4 decreased significantly while HSP-16.2 showed a dose-dependent increase. The decreased expression of GCS-1 and GST-4 implicated the reduced antioxidant ability under BPA exposure, and the increase in SOD-3 expression might be caused by elevated levels of reactive oxygen species (ROS) production. Finally, BPA exposure increased the generation of hydrogen peroxide-related ROS and superoxide anions. Our results suggest that BPA exposure resulted in an accelerated aging process in C. elegans mediated by the induction of oxidative stress.

  9. d-Galactose High-Dose Administration Failed to Induce Accelerated Aging Changes in Neurogenesis, Anxiety, and Spatial Memory on Young Male Wistar Rats

    PubMed Central

    Magano, Sara; Marrana, Francisco; Andrade, José P.

    2015-01-01

    Abstract The model of accelerated senescence with the prolonged administration of d-galactose is used in anti-aging studies because it mimics several aging-associated alterations such as increase of oxidative stress and decline of cognition. However, there is no standardized protocol for this aging model, and recently some reports have questioned its effectiveness. To clarify this issue, we used a model of high-dose d-galactose on 1-month-old male Wistar rats and studied the hippocampus, one of the most affected brain regions. In one group (n = 10), d-galactose was daily administered intraperitoneally (300 mg/kg) during 8 weeks whereas age-matched controls (n = 10) were injected intraperitoneally with saline. A third group (n = 10) was treated with the same dose of d-galactose and with oral epigallocatechin-3-gallate (EGCG) (2 grams/L), a green tea catechin with anti-oxidant and neuroprotective properties. After treatments, animals were submitted to open-field, elevated plus-maze and Morris water maze tests, and neurogenesis in the dentate gyrus subgranular layer was quantified. There were no significant alterations when the three groups were compared in the number of doublecortin- and Ki-67–immunoreactive cells, and also on anxiety levels, spatial learning, and memory. Therefore, d-galactose was not effective in the induction of accelerated aging, and EGCG administered to d-galactose–treated animals did not improve behavior and had no effects on neurogenesis. We conclude that daily 300 mg/kg of d-galactose administered intraperitoneally may not be a suitable model for inducing age-related neurobehavioral alterations in young male Wistar rats. More studies are necessary to obtain a reliable and reproducible model of accelerated senescence in rodents using d-galactose. PMID:25936362

  10. D-Galactose High-Dose Administration Failed to Induce Accelerated Aging Changes in Neurogenesis, Anxiety, and Spatial Memory on Young Male Wistar Rats.

    PubMed

    Cardoso, Armando; Magano, Sara; Marrana, Francisco; Andrade, José P

    2015-12-01

    The model of accelerated senescence with the prolonged administration of d-galactose is used in anti-aging studies because it mimics several aging-associated alterations such as increase of oxidative stress and decline of cognition. However, there is no standardized protocol for this aging model, and recently some reports have questioned its effectiveness. To clarify this issue, we used a model of high-dose d-galactose on 1-month-old male Wistar rats and studied the hippocampus, one of the most affected brain regions. In one group (n = 10), d-galactose was daily administered intraperitoneally (300 mg/kg) during 8 weeks whereas age-matched controls (n = 10) were injected intraperitoneally with saline. A third group (n = 10) was treated with the same dose of d-galactose and with oral epigallocatechin-3-gallate (EGCG) (2 grams/L), a green tea catechin with anti-oxidant and neuroprotective properties. After treatments, animals were submitted to open-field, elevated plus-maze and Morris water maze tests, and neurogenesis in the dentate gyrus subgranular layer was quantified. There were no significant alterations when the three groups were compared in the number of doublecortin- and Ki-67-immunoreactive cells, and also on anxiety levels, spatial learning, and memory. Therefore, d-galactose was not effective in the induction of accelerated aging, and EGCG administered to d-galactose-treated animals did not improve behavior and had no effects on neurogenesis. We conclude that daily 300 mg/kg of d-galactose administered intraperitoneally may not be a suitable model for inducing age-related neurobehavioral alterations in young male Wistar rats. More studies are necessary to obtain a reliable and reproducible model of accelerated senescence in rodents using d-galactose.

  11. A novel assistive method for rigidity evaluation during deep brain stimulation surgery using acceleration sensors.

    PubMed

    Shah, Ashesh; Coste, Jérôme; Lemaire, Jean-Jacques; Schkommodau, Erik; Taub, Ethan; Guzman, Raphael; Derost, Philippe; Hemm, Simone

    2016-12-16

    OBJECTIVE Despite the widespread use of deep brain stimulation (DBS) for movement disorders such as Parkinson's disease (PD), the exact anatomical target responsible for the therapeutic effect is still a subject of research. Intraoperative stimulation tests by experts consist of performing passive movements of the patient's arm or wrist while the amplitude of the stimulation current is increased. At each position, the amplitude that best alleviates rigidity is identified. Intrarater and interrater variations due to the subjective and semiquantitative nature of such evaluations have been reported. The aim of the present study was to evaluate the use of an acceleration sensor attached to the evaluator's wrist to assess the change in rigidity, hypothesizing that such a change will alter the speed of the passive movements. Furthermore, the combined analysis of such quantitative results with anatomy would generate a more reproducible description of the most effective stimulation sites. METHODS To test the reliability of the method, it was applied during postoperative follow-up examinations of 3 patients. To study the feasibility of intraoperative use, it was used during 9 bilateral DBS operations in patients suffering from PD. Changes in rigidity were calculated by extracting relevant outcome measures from the accelerometer data. These values were used to identify rigidity-suppressing stimulation current amplitudes, which were statistically compared with the amplitudes identified by the neurologist. Positions for the chronic DBS lead implantation that would have been chosen based on the acceleration data were compared with clinical choices. The data were also analyzed with respect to the anatomical location of the stimulating electrode. RESULTS Outcome measures extracted from the accelerometer data were reproducible for the same evaluator, thus providing a reliable assessment of rigidity changes during intraoperative stimulation tests. Of the 188 stimulation sites

  12. Fat-specific Dicer deficiency accelerates aging and mitigates several effects of dietary restriction in mice

    PubMed Central

    Reis, Felipe C. G.; Branquinho, Jéssica L. O.; Brandão, Bruna B.; Guerra, Beatriz A.; Silva, Ismael D.; Frontini, Andrea; Thomou, Thomas; Sartini, Loris; Cinti, Saverio; Kahn, C. Ronald; Festuccia, William T.; Kowaltowski, Alicia J.; Mori, Marcelo A.

    2016-01-01

    Aging increases the risk of type 2 diabetes, and this can be prevented by dietary restriction (DR). We have previously shown that DR inhibits the downregulation of miRNAs and their processing enzymes - mainly Dicer - that occurs with aging in mouse white adipose tissue (WAT). Here we used fat-specific Dicer knockout mice (AdicerKO) to understand the contributions of adipose tissue Dicer to the metabolic effects of aging and DR. Metabolomic data uncovered a clear distinction between the serum metabolite profiles of Lox control and AdicerKO mice, with a notable elevation of branched-chain amino acids (BCAA) in AdicerKO. These profiles were associated with reduced oxidative metabolism and increased lactate in WAT of AdicerKO mice and were accompanied by structural and functional changes in mitochondria, particularly under DR. AdicerKO mice displayed increased mTORC1 activation in WAT and skeletal muscle, where Dicer expression is not affected. This was accompanied by accelerated age-associated insulin resistance and premature mortality. Moreover, DR-induced insulin sensitivity was abrogated in AdicerKO mice. This was reverted by rapamycin injection, demonstrating that insulin resistance in AdicerKO mice is caused by mTORC1 hyperactivation. Our study evidences a DR-modulated role for WAT Dicer in controlling metabolism and insulin resistance. PMID:27241713

  13. A long-standing hyperglycaemic condition impairs skin barrier by accelerating skin ageing process.

    PubMed

    Park, Hwa-Young; Kim, Jae-Hong; Jung, Minyoung; Chung, Choon Hee; Hasham, Rosnani; Park, Chang Seo; Choi, Eung Ho

    2011-12-01

    Uncontrolled chronic hyperglycaemia including type 2 diabetes mellitus (DM) induces many skin problems related to chronic impaired skin barrier state. However, little is known about the skin barrier state of chronic hyperglycaemia patients, the dysfunction of which may be a major cause of their skin problems. In this study, we investigated whether a long-standing hyperglycaemic condition including type 2 DM impairs skin barrier homoeostasis in proportion to the duration and its pathomechanism. We utilized the Otsuka Long-Evans Tokushima Fatty (OLETF) rats as an animal model of long-standing hyperglycaemia and Long-Evans Tokushima Otsuka rats as a control strain. We confirmed that a long-standing hyperglycaemia delayed skin barrier homoeostasis, which correlated with haemoglobin A1c levels. OLETF rats as a long-standing hyperglycaemia model exhibited decreased epidermal lipid synthesis and antimicrobial peptide expression with increasing age. Decreased epidermal lipid synthesis accounted for decreased lamellar body production. In addition, OLETF rats had significantly higher serum levels of advanced glycation end products (AGEs) and elevated levels of the receptor for AGE in the epidermis. A long-standing hyperglycaemic condition impairs skin barrier function including permeability and antimicrobial barriers by accelerating skin ageing process in proportion to the duration of hyperglycaemia, which could be a major pathophysiology underlying cutaneous complications of DM.

  14. Aging brain microenvironment decreases hippocampal neurogenesis through Wnt-mediated survivin signaling.

    PubMed

    Miranda, Carlos J; Braun, Lyndsey; Jiang, Yuying; Hester, Mark E; Zhang, Ling; Riolo, Matthew; Wang, Haijuan; Rao, Meghan; Altura, Rachel A; Kaspar, Brian K

    2012-06-01

    Accumulating evidence suggests that adult hippocampal neurogenesis relies on the controlled and continued proliferation of neural progenitor cells (NPCs). With age, neurogenesis decreases through mechanisms that remain unclear but are believed to involve changes in the NPC microenvironment. Here, we provide evidence that NPC proliferation in the adult brain is in part regulated by astrocytes via Wnt signaling and that this cellular cross-talk is modified in the aging brain, leading to decreased proliferation of NPCs. Furthermore, we show that astrocytes regulate the NPC cell cycle by acting on the expression levels of survivin, a known mitotic regulator. Among cell cycle genes found down-regulated in aged NPCs, survivin was the only one that restored NPC proliferation in the aged brain. Our results provide a mechanism for the gradual loss of neurogenesis in the brain associated with aging and suggest that targeted modulation of survivin expression directly or through Wnt signaling could be used to stimulate adult neurogenesis.

  15. Aging Shapes the Population-Mean and -Dispersion of Gene Expression in Human Brains

    PubMed Central

    Brinkmeyer-Langford, Candice L.; Guan, Jinting; Ji, Guoli; Cai, James J.

    2016-01-01

    Human aging is associated with cognitive decline and an increased risk of neurodegenerative disease. Our objective for this study was to evaluate potential relationships between age and variation in gene expression across different regions of the brain. We analyzed the Genotype-Tissue Expression (GTEx) data from 54 to 101 tissue samples across 13 brain regions in post-mortem donors of European descent aged between 20 and 70 years at death. After accounting for the effects of covariates and hidden confounding factors, we identified 1446 protein-coding genes whose expression in one or more brain regions is correlated with chronological age at a false discovery rate of 5%. These genes are involved in various biological processes including apoptosis, mRNA splicing, amino acid biosynthesis, and neurotransmitter transport. The distribution of these genes among brain regions is uneven, suggesting variable regional responses to aging. We also found that the aging response of many genes, e.g., TP37 and C1QA, depends on individuals' genotypic backgrounds. Finally, using dispersion-specific analysis, we identified genes such as IL7R, MS4A4E, and TERF1/TERF2 whose expressions are differentially dispersed by aging, i.e., variances differ between age groups. Our results demonstrate that age-related gene expression is brain region-specific, genotype-dependent, and associated with both mean and dispersion changes. Our findings provide a foundation for more sophisticated gene expression modeling in the studies of age-related neurodegenerative diseases. PMID:27536236

  16. Caveolin-1 and Accelerated Host Aging in the Breast Tumor Microenvironment

    PubMed Central

    Mercier, Isabelle; Camacho, Jeanette; Titchen, Kanani; Gonzales, Donna M.; Quann, Kevin; Bryant, Kelly G.; Molchansky, Alexander; Milliman, Janet N.; Whitaker-Menezes, Diana; Sotgia, Federica; Jasmin, Jean-François; Schwarting, Roland; Pestell, Richard G.; Blagosklonny, Mikhail V.; Lisanti, Michael P.

    2013-01-01

    Increasing chronological age is the most significant risk factor for human cancer development. To examine the effects of host aging on mammary tumor growth, we used caveolin (Cav)-1 knockout mice as a bona fide model of accelerated host aging. Mammary tumor cells were orthotopically implanted into these distinct microenvironments (Cav-1+/+ versus Cav-1−/− age-matched young female mice). Mammary tumors grown in a Cav-1–deficient tumor microenvironment have an increased stromal content, with vimentin-positive myofibroblasts (a marker associated with oxidative stress) that are also positive for S6-kinase activation (a marker associated with aging). Mammary tumors grown in a Cav-1–deficient tumor microenvironment were more than fivefold larger than tumors grown in a wild-type microenvironment. Thus, a Cav-1–deficient tumor microenvironment provides a fertile soil for breast cancer tumor growth. Interestingly, the mammary tumor-promoting effects of a Cav-1–deficient microenvironment were estrogen and progesterone independent. In this context, chemoprevention was achieved by using the mammalian target of rapamycin (mTOR) inhibitor and anti-aging drug, rapamycin. Systemic rapamycin treatment of mammary tumors grown in a Cav-1–deficient microenvironment significantly inhibited their tumor growth, decreased their stromal content, and reduced the levels of both vimentin and phospho-S6 in Cav-1–deficient cancer-associated fibroblasts. Since stromal loss of Cav-1 is a marker of a lethal tumor microenvironment in breast tumors, these high-risk patients might benefit from treatment with mTOR inhibitors, such as rapamycin or other rapamycin-related compounds (rapalogues). PMID:22698676

  17. Profiling of methylation and demethylation pathways during brain development and ageing.

    PubMed

    Kraus, Theo F J; Kilinc, Selma; Steinmaurer, Martina; Stieglitz, Marc; Guibourt, Virginie; Kretzschmar, Hans A

    2016-03-01

    Numerous signal pathways are epigenetically controlled during brain development and ageing. Thereby, both 5-methylcytosine (5mC) and the newly described 5-hydroxymethylcytosine (5hmC) are highly exhibited in the brain. As there is an uneven distribution of 5hmC in the brain depending on age and region, there is the need to investigate the underlying mechanisms being responsible for 5hmC generation and decline. The aim of this study was to quantify expression levels of genes that are associated with DNA methylation/demethylation in different brain regions and at different ages. Therefore, we investigated frontal cortex and cerebellum of 40 mice (strain C57BL/6), each eight mice sacrificed at day 0, 7, 15, 30 and 120 after birth. We performed expression profiling of methylation/demethylation genes depending on age and brain region. Interestingly, we see significant expression differences of genes being responsible for methylation/demethylation with a significant reduction of expression levels during ageing. Validating selected expression data on protein level using immunohistochemistry verified the expression data. In conclusion, our findings demonstrate that the regulation of methylation/demethylation pathways is highly controlled depending on brain region and age. Thus our data will help to better understand the complexity and plasticity of the brain epigenome.

  18. 3D spatially encoded and accelerated TE-averaged echo planar spectroscopic imaging in healthy human brain.

    PubMed

    Iqbal, Zohaib; Wilson, Neil E; Thomas, M Albert

    2016-03-01

    Several different pathologies, including many neurodegenerative disorders, affect the energy metabolism of the brain. Glutamate, a neurotransmitter in the brain, can be used as a biomarker to monitor these metabolic processes. One method that is capable of quantifying glutamate concentration reliably in several regions of the brain is TE-averaged (1) H spectroscopic imaging. However, this type of method requires the acquisition of multiple TE lines, resulting in long scan durations. The goal of this experiment was to use non-uniform sampling, compressed sensing reconstruction and an echo planar readout gradient to reduce the scan time by a factor of eight to acquire TE-averaged spectra in three spatial dimensions. Simulation of glutamate and glutamine showed that the 2.2-2.4 ppm spectral region contained 95% glutamate signal using the TE-averaged method. Peak integration of this spectral range and home-developed, prior-knowledge-based fitting were used for quantitation. Gray matter brain phantom measurements were acquired on a Siemens 3 T Trio scanner. Non-uniform sampling was applied retrospectively to these phantom measurements and quantitative results of glutamate with respect to creatine 3.0 (Glu/Cr) ratios showed a coefficient of variance of 16% for peak integration and 9% for peak fitting using eight-fold acceleration. In vivo scans of the human brain were acquired as well and five different brain regions were quantified using the prior-knowledge-based algorithm. Glu/Cr ratios from these regions agreed with previously reported results in the literature. The method described here, called accelerated TE-averaged echo planar spectroscopic imaging (TEA-EPSI), is a significant methodological advancement and may be a useful tool for categorizing glutamate changes in pathologies where affected brain regions are not known a priori. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Increased recruitment of bone marrow-derived cells into the brain associated with altered brain cytokine profile in senescence-accelerated mice.

    PubMed

    Hasegawa-Ishii, Sanae; Inaba, Muneo; Li, Ming; Shi, Ming; Umegaki, Hiroyuki; Ikehara, Susumu; Shimada, Atsuyoshi

    2016-04-01

    Bone marrow-derived cells enter the brain in a non-inflammatory condition through the attachments of choroid plexus and differentiate into ramified myeloid cells. Neurodegenerative conditions may be associated with altered immune-brain interaction. The senescence-accelerated mouse prone 10 (SAMP10) undergoes earlier onset neurodegeneration than C57BL/6 (B6) strain. We hypothesized that the dynamics of immune cells migrating from the bone marrow to the brain is perturbed in SAMP10 mice. We created 4 groups of radiation chimeras by intra-bone marrow-bone marrow transplantation using 2-month-old (2 mo) and 10 mo SAMP10 and B6 mice as recipients with GFP transgenic B6 mice as donors, and analyzed histologically 4 months later. In the [B6 → 10 mo SAMP10] chimeras, more ramified marrow-derived cells populated a larger number of discrete brain regions than the other chimeras, especially in the diencephalon. Multiplex cytokine assays of the diencephalon prepared from non-treated 3 mo and 12 mo SAMP10 and B6 mice revealed that 12 mo SAMP10 mice exhibited higher tissue concentrations of CXCL1, CCL11, G-CSF, CXCL10 and IL-6 than the other groups. Immunohistologically, choroid plexus epithelium and ependyma produced CXCL1, while astrocytic processes in the attachments of choroid plexus expressed CCL11 and G-CSF. The median eminence produced CXCL10, hypothalamic neurons G-CSF and tanycytes CCL11 and G-CSF. These brain cytokine profile changes in 12 mo SAMP10 mice were likely to contribute to acceleration of the dynamics of marrow-derived cells to the diencephalon. Further studies on the functions of ramified marrow-derived myeloid cells would enhance our understanding of the brain-bone marrow interaction.

  20. Evaluation of oxidative behavior of polyolefin geosynthetics utilizing accelerated aging tests based on temperature and pressure

    NASA Astrophysics Data System (ADS)

    Li, Mengjia

    Polyolefin geosynthetics are susceptible to oxidation, which eventually leads to the reduction in their engineering properties. In the application of polyolefin geosynthetics, a major issue is an estimate of the materials durability (i.e. service lifetime) under various aging conditions. Antioxidant packages are added to the polyolefin products to extend the induction time, during which antioxidants are gradually depleted and polymer oxidation reactions are prevented. In this PhD study, an improved laboratory accelerating aging method under elevated and high pressure environments was applied to evaluate the combined effect of temperature and pressure on the depletion of the antioxidants and the oxidation of polymers. Four types of commercial polyolefn geosynthetic materials selected for aging tests included HDPE geogrid, polypropylene woven and nonwoven geotextiles. A total of 33 different temperature/pressure aging conditions were used, with the incubation duration up to 24 months. The applied oven temperature ranged from 35°C to 105°C and the partial oxygen pressure ranged from 0.005 MPa to 6.3 MPa. Using the Oxidative Induction Time (OIT) test, the antioxidant depletion, which is correlated to the decrease of the OIT value, was found to follow apparent first-order decay. The OIT data also showed that, the antioxidant depletion rate increased with temperature according to the Arrhenius equation, while under constant temperatures, the rate increased exponentially with the partial pressure of oxygen. A modified Arrhenius model was developed to fit the antioxidant depletion rate as a function of temperature and pressure and to predict the antioxidant lifetime under various field conditions. This study has developed new temperature/pressure incubation aging test method with lifetime prediction models. Using this new technique, the antioxidant lifetime prediction results are close to regular temperature aging data while the aging duration can be reduced considerably

  1. Association of structural global brain network properties with intelligence in normal aging.

    PubMed

    Fischer, Florian U; Wolf, Dominik; Scheurich, Armin; Fellgiebel, Andreas

    2014-01-01

    Higher general intelligence attenuates age-associated cognitive decline and the risk of dementia. Thus, intelligence has been associated with cognitive reserve or resilience in normal aging. Neurophysiologically, intelligence is considered as a complex capacity that is dependent on a global cognitive network rather than isolated brain areas. An association of structural as well as functional brain network characteristics with intelligence has already been reported in young adults. We investigated the relationship between global structural brain network properties, general intelligence and age in a group of 43 cognitively healthy elderly, age 60-85 years. Individuals were assessed cross-sectionally using Wechsler Adult Intelligence Scale-Revised (WAIS-R) and diffusion-tensor imaging. Structural brain networks were reconstructed individually using deterministic tractography, global network properties (global efficiency, mean shortest path length, and clustering coefficient) were determined by graph theory and correlated to intelligence scores within both age groups. Network properties were significantly correlated to age, whereas no significant correlation to WAIS-R was observed. However, in a subgroup of 15 individuals aged 75 and above, the network properties were significantly correlated to WAIS-R. Our findings suggest that general intelligence and global properties of structural brain networks may not be generally associated in cognitively healthy elderly. However, we provide first evidence of an association between global structural brain network properties and general intelligence in advanced elderly. Intelligence might be affected by age-associated network deterioration only if a certain threshold of structural degeneration is exceeded. Thus, age-associated brain structural changes seem to be partially compensated by the network and the range of this compensation might be a surrogate of cognitive reserve or brain resilience.

  2. Age-dependent effect of static magnetic field on brain tissue hydration.

    PubMed

    Deghoyan, Anush; Nikoghosyan, Anna; Heqimyan, Armenuhi; Ayrapetyan, Sinerik

    2014-01-01

    Age-dependent effect of Static Magnetic Field (SMF) on rats in a condition of active and inactive Na(+)/K(+) pump was studied for comparison of brain tissues hydration state changes and magnetic sensitivity. Influence of 15 min 0, 2 Tesla (T) SMF on brain tissue hydration of three aged groups of male albino rats was studied. Tyrode's physiological solution and 10(-4) M ouabain was used for intraperitoneal injections. For animal immobilization, the liquid nitrogen was used and the definition of tissue water content was performed by tissue drying method. Initial water content in brain tissues of young animals is significantly higher than in those of adult and aged ones. SMF exposure leads to decrease of water content in brain tissues of young animals and increase in brain tissues of adult and aged ones. In case of ouabain-poisoned animals, SMF gives reversal effects on brain tissue's hydration both in young and aged animals, while no significant effect on adults is observed. It is suggested that initial state of tissue hydration could play a crucial role in animal age-dependent magnetic sensitivity and the main reason for this could be age-dependent dysfunction of Na(+)/K(+) pump.

  3. Brain volumetric changes and cognitive ageing during the eighth decade of life

    PubMed Central

    Dickie, David Alexander; Cox, Simon R.; Valdes Hernandez, Maria del C.; Corley, Janie; Royle, Natalie A.; Pattie, Alison; Aribisala, Benjamin S.; Redmond, Paul; Muñoz Maniega, Susana; Taylor, Adele M.; Sibbett, Ruth; Gow, Alan J.; Starr, John M.; Bastin, Mark E.; Wardlaw, Joanna M.; Deary, Ian J.

    2015-01-01

    Abstract Later‐life changes in brain tissue volumes—decreases in the volume of healthy grey and white matter and increases in the volume of white matter hyperintensities (WMH)—are strong candidates to explain some of the variation in ageing‐related cognitive decline. We assessed fluid intelligence, memory, processing speed, and brain volumes (from structural MRI) at mean age 73 years, and at mean age 76 in a narrow‐age sample of older individuals (n = 657 with brain volumetric data at the initial wave, n = 465 at follow‐up). We used latent variable modeling to extract error‐free cognitive levels and slopes. Initial levels of cognitive ability were predictive of subsequent brain tissue volume changes. Initial brain volumes were not predictive of subsequent cognitive changes. Brain volume changes, especially increases in WMH, were associated with declines in each of the cognitive abilities. All statistically significant results were modest in size (absolute r‐values ranged from 0.114 to 0.334). These results build a comprehensive picture of macrostructural brain volume changes and declines in important cognitive faculties during the eighth decade of life. Hum Brain Mapp 36:4910–4925, 2015. © 2015 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc PMID:26769551

  4. Wear resistance of highly cross-linked and remelted polyethylenes after ion implantation and accelerated ageing.

    PubMed

    Medel, F J; Puértolas, J A

    2008-08-01

    Ion implantation may provide medical polyethylenes with excellent mechanical and tribological properties, helping to lower the risk of long-term osteolysis. Highly crosslinked and remelted polyethylenes, materials currently used as soft components in artificial joints, were implanted with N+ and He+ ions at different ion fluences. The mechanical and tribological properties under distilled water lubrication at body temperature were assessed after ion implantation by means of microhardness and pin-on-disc tests respectively. Thus, the influences of the ionic species and implantation dose on surface hardness, friction coefficient, and wear factor were fully characterized. Furthermore, the tribological behaviour was evaluated after an accelerated ageing protocol (120 degrees C for 36h). Ion implantation increased the surface hardness, as well as friction coefficients, and decreased the wear factors especially at the highest doses. Also, even though all artificially aged materials showed a worse wear behaviour, polyethylenes implanted with either N+ or He+ at the highest doses maintained a relatively good wear factor in comparison with the aged non-implanted material. The origins of these modifications are discussed according to the effects of ion implantation on the microstructure of the polymer.

  5. The glia doctrine: addressing the role of glial cells in healthy brain ageing.

    PubMed

    Nagelhus, Erlend A; Amiry-Moghaddam, Mahmood; Bergersen, Linda H; Bjaalie, Jan G; Eriksson, Jens; Gundersen, Vidar; Leergaard, Trygve B; Morth, J Preben; Storm-Mathisen, Jon; Torp, Reidun; Walhovd, Kristine B; Tønjum, Tone

    2013-10-01

    Glial cells in their plurality pervade the human brain and impact on brain structure and function. A principal component of the emerging glial doctrine is the hypothesis that astrocytes, the most abundant type of glial cells, trigger major molecular processes leading to brain ageing. Astrocyte biology has been examined using molecular, biochemical and structural methods, as well as 3D brain imaging in live animals and humans. Exosomes are extracelluar membrane vesicles that facilitate communication between glia, and have significant potential for biomarker discovery and drug delivery. Polymorphisms in DNA repair genes may indirectly influence the structure and function of membrane proteins expressed in glial cells and predispose specific cell subgroups to degeneration. Physical exercise may reduce or retard age-related brain deterioration by a mechanism involving neuro-glial processes. It is most likely that additional information about the distribution, structure and function of glial cells will yield novel insight into human brain ageing. Systematic studies of glia and their functions are expected to eventually lead to earlier detection of ageing-related brain dysfunction and to interventions that could delay, reduce or prevent brain dysfunction.

  6. Intraneuronal protein aggregation as a trigger for inflammation and neurodegeneration in the aging brain.

    PubMed

    Currais, Antonio; Fischer, Wolfgang; Maher, Pamela; Schubert, David

    2017-01-01

    Age is, by far, the greatest risk factor for Alzheimer's disease (AD), yet few AD drug candidates have been generated that target pathways specifically associated with the aging process itself. Two ubiquitous features of the aging brain are the intracellular accumulation of aggregated proteins and inflammation. As intraneuronal amyloid protein is detected before markers of inflammation, we argue that old, age-associated, aggregated proteins in neurons can induce inflammation, resulting in multiple forms of brain toxicities. The consequence is the increased risk of old, age-associated, neurodegenerative diseases. As most of these diseases are associated with the accumulation of aggregated proteins, it is possible that any therapeutic that reduces intracellular protein aggregation will benefit all.-Currais, A., Fischer, W., Maher, P., Schubert, D. Intraneuronal protein aggregation as a trigger for inflammation and neurodegeneration in the aging brain.

  7. Age-associated losses of brain volume predict longitudinal cognitive declines over 8 to 20 years.

    PubMed

    Rabbitt, Patrick; Ibrahim, Said; Lunn, Mary; Scott, Marietta; Thacker, Neil; Hutchinson, Charles; Horan, Michael; Pendleton, Neil; Jackson, Alan

    2008-01-01

    Absolute differences in global brain volume predict differences in cognitive ability among healthy older adults. However, absolute differences confound lifelong differences in brain size with amounts of age-related shrinkage. Measurements of cerebrospinal fluid (CSF) volume were made to estimate age-related shrinkage in 93 healthy volunteers aged 63 to 86 years. Their current levels of brain shrinkage predicted their amounts of decline over the previous 8 to 20 years on repeated assessments during a longitudinal study on the Cattell "Culture Fair" Intelligence Test, on two tests of information processing speed, and marginally on the Wechsler Adult Intelligence Scale (D. Wechsler, 1981), but not on three memory tests. Loss of brain volume is an effective marker both for current cognitive status and for amounts and rates of previous age-related cognitive losses.

  8. Neuro-immune Dysfunction During Brain Aging: New Insights in Microglial Cell Regulation

    PubMed Central

    Matt, Stephanie M.; Johnson, Rodney W.

    2015-01-01

    Microglia, the resident immune cells of the brain, are at the center of communication between the central nervous system and immune system. While these brain-immune interactions are balanced in healthy adulthood, the ability to maintain homeostasis during aging is impaired. Microglia develop a loss of integrated regulatory networks including aberrant signaling from other brain cells, immune sensors, and epigenetic modifiers. The low-grade chronic neuroinflammation associated with this dysfunctional activity likely contributes to cognitive deficits and susceptibility to age-related pathologies. A better understanding of the underlying mechanisms responsible for neuro-immune dysregulation with age is crucial for providing targeted therapeutic strategies to support brain repair and healthy aging. PMID:26595306

  9. From randomly accelerated particles to Lévy walks: non-ergodic behavior and aging

    NASA Astrophysics Data System (ADS)

    Radons, Guenter; Albers, Tony; Institute of Physics, Complex Systems; Nonlinear Dynamics Team

    For randomly accelerated particles we detected, and were able to analyze in detail (PRL 113, 184101 (2014)), the phenomenon of weak-ergodicity breaking (WEB), i.e. the inequivalence of ensemble- and time-averaged mean-squared displacements (MSD). These results, including their aging time dependence, are relevant for anomalous chaotic diffusion in Hamiltonian systems, for passive tracer transport in turbulent flows, and many other systems showing momentum diffusion. There are, however, several related models, such as the integrated random excursion model, or, space-time correlated Lévy walks and flights, with similar statistical behavior. We compare the WEB related properties of these models and find surprising differences although, for equivalent parameters, all of them are supposed to lead to the same ensemble-averaged MSD. Our findings are relevant for distinguishing possible models for the anomalous diffusion occurring in experimental situations.

  10. Evaluation of Experimental Parameters in the Accelerated Aging of Closed-Cell Foam Insulation

    SciTech Connect

    Stovall, Therese K; Vanderlan, Michael; Atchley, Jerald Allen

    2012-12-01

    The thermal conductivity of many closed-cell foam insulation products changes over time as production gases diffuse out of the cell matrix and atmospheric gases diffuse into the cells. Thin slicing has been shown to be an effective means of accelerating this process in such a way as to produce meaningful results. Efforts to produce a more prescriptive version of the ASTM C1303 standard test method led to the ruggedness test described here. This test program included the aging of full size insulation specimens for time periods of five years for direct comparison to the predicted results. Experimental parameters under investigation include: slice thickness, slice origin (at the surface or from the core of the slab), thin slice stack composition, product facings, original product thickness, product density, and product type. The test protocol has been completed and this report provides a detailed evaluation of the impact of the test parameters on the accuracy of the 5-year thermal conductivity prediction.

  11. Effect of disinfection and accelerated ageing on dimensional stability and detail reproduction of a facial silicone with nanoparticles.

    PubMed

    Pesqueira, A A; Goiato, M C; Dos Santos, D M; Haddad, M F; Moreno, A

    2012-05-01

    The aim of the present study was to evaluate the effect of disinfection and accelerated ageing on the dimensional stability and detail reproduction of a facial silicone with different types of nanoparticle. A total of 60 specimens were fabricated with Silastic MDX 4-4210 silicone and they were divided into three groups: colourless and pigmented with nanoparticles (make-up powder and ceramic powder). Half of the specimens of each group were disinfected with Efferdent tablets and half with neutral soap for 60 days. Afterwards, all specimens were subjected to accelerated ageing. Both dimensional stability and detail reproduction tests were performed after specimen fabrication (initial period), after chemical disinfection, and after accelerated ageing periods (252, 504 and 1008 hours). The dimensional stability test was conducted using AutoCAD software, while detail reproduction was analysed using a stereoscope magnifying glass. Dimensional stability values were statistically evaluated by analysis of variance (ANOVA) followed by Tukey's test (p < 0.01). Detail reproduction results were compared using a score. Chemical disinfection and also accelerated ageing affected the dimensional stability of the facial silicone with statistically significant results. The silicone's detail reproduction was not affected by these two factors regardless of nanoparticle type, disinfection and accelerated ageing.

  12. Astrocytes in the aging brain express characteristics of senescence-associated secretory phenotype.

    PubMed

    Salminen, Antero; Ojala, Johanna; Kaarniranta, Kai; Haapasalo, Annakaisa; Hiltunen, Mikko; Soininen, Hilkka

    2011-07-01

    Cellular stress increases progressively with aging in mammalian tissues. Chronic stress triggers several signaling cascades that can induce a condition called cellular senescence. Recent studies have demonstrated that senescent cells express a senescence-associated secretory phenotype (SASP). Emerging evidence indicates that the number of cells expressing biomarkers of cellular senescence increases in tissues with aging, which implies that cellular senescence is an important player in organismal aging. In the brain, the aging process is associated with degenerative changes, e.g. synaptic loss and white matter atrophy, which lead to progressive cognitive impairment. There is substantial evidence for the presence of oxidative, proteotoxic and metabolic stresses in aging brain. A low-level, chronic inflammatory process is also present in brain during aging. Astrocytes demonstrate age-related changes that resemble those of the SASP: (i) increased level of intermediate glial fibrillary acidic protein and vimentin filaments, (ii) increased expression of several cytokines and (iii) increased accumulation of proteotoxic aggregates. In addition, in vitro stress evokes a typical senescent phenotype in cultured astrocytes and, moreover, isolated astrocytes from aged brain display the proinflammatory phenotype. All of these observations indicate that astrocytes are capable of triggering the SASP and the astrocytes in aging brain display typical characteristics of cellular senescence. Bearing in mind the many functions of astrocytes, it is evident that the age-related senescence of astrocytes enhances the decline in functional capacity of the brain. We will review the astroglial changes occurring during aging and emphasize that senescent astrocytes can have an important role in age-related neuroinflammation and neuronal degeneration.

  13. Comparative Study on Accelerated Thermal Ageing of Vegetable Insulating Oil-paperboard and Mineral Oil-paperboard

    NASA Astrophysics Data System (ADS)

    Zhou, Zhu-Jun; Hu, Ting; Cheng, Lin; Tian, Kai; Yang, Jun; Wang, Xuan; Fang, Fu-Xin; Kong, Hai-Yang; Qian, Hang

    2016-05-01

    To comparatively study the insulation ageing life of vegetable insulating oil-paperboard and mineral oil-paperboard, we conducted accelerated thermal ageing experiments at 170°C. Then according to the temperature rise of vegetable insulating oil transformer, we conducted accelerated thermal ageing experiments at 150°C for vegetable insulating oil-paperboard and at 140°C for mineral oil-paperboard. The appearance, polymerization degree, and SEM microstructure of the paperboard after different ageing experiments were comparative analyzed. The results show that after the oil-paperboard system is accelerated ageing for 1 000 h at 170°C, that is equivalent to 20 years natural ageing, the structure of paperboard in vegetable insulating oil is damaged severely, which indicates that the lifetime of transformer are in the late stage; while the structure of paperboard in mineral oil maintain complete, and the polymerization degree is still above 500, which indicate that the lifetime of transformer are in the middle stage. The accelerated ageing rate of the vegetable insulating oil-paperboard system at 150°C is slower than that of the mineral oil-paperboard system, which indicates that the lifetime of the vegetable insulating oil-paperboard is longer than that of the mineral oil-paperboard.

  14. Gestational Age and Neonatal Brain Microstructure in Term Born Infants: A Birth Cohort Study

    PubMed Central

    Broekman, Birit F. P.; Wang, Changqing; Li, Yue; Rifkin-Graboi, Anne; Saw, Seang Mei; Chong, Yap-Seng; Kwek, Kenneth; Gluckman, Peter D.; Fortier, Marielle V.; Meaney, Michael J.; Qiu, Anqi

    2014-01-01

    Objective Understanding healthy brain development in utero is crucial in order to detect abnormal developmental trajectories due to developmental disorders. However, in most studies neuroimaging was done after a significant postnatal period, and in those studies that performed neuroimaging on fetuses, the quality of data has been affected due to complications of scanning during pregnancy. To understand healthy brain development between 37–41 weeks of gestational age, our study assessed the in utero growth of the brain in healthy term born babies with DTI scanning soon after birth. Methods A cohort of 93 infants recruited from maternity hospitals in Singapore underwent diffusion tensor imaging between 5 to 17 days after birth. We did a cross-sectional examination of white matter microstructure of the brain among healthy term infants as a function of gestational age via voxel-based analysis on fractional anisotropy. Results Greater gestational age at birth in term infants was associated with larger fractional anisotropy values in early developing brain regions, when corrected for age at scan. Specifically, it was associated with a cluster located at the corpus callosum (corrected p<0.001), as well as another cluster spanning areas of the anterior corona radiata, anterior limb of internal capsule, and external capsule (corrected p<0.001). Conclusions Our findings show variation in brain maturation associated with gestational age amongst ‘term’ infants, with increased brain maturation when born with a relatively higher gestational age in comparison to those infants born with a relatively younger gestational age. Future studies should explore if these differences in brain maturation between 37 and 41 weeks of gestational age will persist over time due to development outside the womb. PMID:25535959

  15. Mutant alpha-synuclein causes age-dependent neuropathology in monkey brain.

    PubMed

    Yang, Weili; Wang, Guohao; Wang, Chuan-En; Guo, Xiangyu; Yin, Peng; Gao, Jinquan; Tu, Zhuchi; Wang, Zhengbo; Wu, Jing; Hu, Xintian; Li, Shihua; Li, Xiao-Jiang

    2015-05-27

    Parkinson's disease (PD) is an age-dependent neurodegenerative disease that often occurs in those over age 60. Although rodents and small animals have been used widely to model PD and investigate its pathology, their short life span makes it difficult to assess the aging-related pathology that is likely to occur in PD patient brains. Here, we used brain tissues from rhesus monkeys at 2-3, 7-8, and >15 years of age to examine the expression of Parkin, PINK1, and α-synuclein, which are known to cause PD via loss- or gain-of-function mechanisms. We found that α-synuclein is increased in the older monkey brains, whereas Parkin and PINK1 are decreased or remain unchanged. Because of the gain of toxicity of α-synuclein, we performed stereotaxic injection of lentiviral vectors expressing mutant α-synuclein (A53T) into the substantia nigra of monkeys and found that aging also increases the accumulation of A53T in neurites and its associated neuropathology. A53T also causes more extensive reactive astrocytes and axonal degeneration in monkey brain than in mouse brain. Using monkey brain tissues, we found that A53T interacts with neurofascin, an adhesion molecule involved in axon subcellular targeting and neurite outgrowth. Aged monkey brain tissues show an increased interaction of neurofascin with A53T. Overexpression of A53T causes neuritic toxicity in cultured neuronal cells, which can be attenuated by transfected neurofascin. These findings from nonhuman primate brains reveal age-dependent pathological and molecular changes that could contribute to the age-dependent neuropathology in PD.

  16. Effect of aging and damage on the brain modelled by a phase transition

    NASA Astrophysics Data System (ADS)

    Miyazima, Sasuke; Sakakibara, Mitsuharu

    1992-03-01

    Aging and the effects of damage on the brain are considered on the basis of the Hopfield model. As the damage to the brain or the debility of neurons is increased by aging, a sudden change similar to critical phenomena is observed in the ability to retrieve information or in recognition. This type of critical behavior is very similar to the percolation phenomenon in physics. Furthermore the relearning effect, which corresponds to so-called rehabilitation, is discussed.

  17. Gene expression changes with age in skin, adipose tissue, blood and brain

    PubMed Central

    2013-01-01

    Background Previous studies have demonstrated that gene expression levels change with age. These changes are hypothesized to influence the aging rate of an individual. We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years. Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age. Results Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue. Only two genes expressed in lymphoblastoid cell lines showed significant changes with age. Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years. We identified only one age-related gene common to the three tissues. There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues. Conclusions Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing. A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues. More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases. PMID:23889843

  18. Transcranial magnetic stimulation of degenerating brain: a comparison of normal aging, Alzheimer's, Parkinson's and Huntington's disease.

    PubMed

    Ljubisavljevic, M R; Ismail, F Y; Filipovic, S

    2013-07-01

    Although the brain's ability to change constantly in response to external and internal inputs is now well recognized the mechanisms behind it in normal aging and neurodegeneration are less well understood. To gain a better understanding, transcranial magnetic stimulation (TMS) has been used extensively to characterize non-invasively the cortical neurophysiology of the aging and degenerating brain. Furthermore, there has been a surge of studies examining whether repetitive TMS (rTMS) can be used to improve functional deficits in various conditions including normal aging, Alzheimer's and Parkinson's disease. The results of these studies in normal aging and neurodegeneration have emerged reasonably coherent in delineating the main pathology in spite of considerable technical limitations, omnipresent methodological variability, and extraordinary patient heterogeneity. Nevertheless, comparing and integrating what is known about TMS measurements of cortical excitability and plasticity in disorders that predominantly affect cortical brain structures with disorders that predominantly affect subcortical brain structures may provide better understanding of normal and abnormal brain aging fostering new. The present review provides a TMS perspective of changes in cortical neurophysiology and neurochemistry in normal aging and neurodegeneration by integrating what is revealed in individual TMS measurements of cortical excitability and plasticity in physiological aging, Alzheimer's, Parkinson's, and Huntington's, disease. The paper also reflects on current developments in utilizing TMS as a physiologic biomarker to discriminate physiologic aging from neurodegeneration and its potential as a method of therapeutic intervention.

  19. Changes in topological organization of functional PET brain network with normal aging.

    PubMed

    Liu, Zhiliang; Ke, Lining; Liu, Huafeng; Huang, Wenhua; Hu, Zhenghui

    2014-01-01

    Recent studies about brain network have suggested that normal aging is associated with alterations in coordinated patterns of the large-scale brain functional and structural systems. However, age-related changes in functional networks constructed via positron emission tomography (PET) data are still barely understood. Here, we constructed functional brain networks composed of 90 regions in younger (mean age 36.5 years) and older (mean age 56.3 years) age groups with PET data. 113 younger and 110 older healthy individuals were separately selected for two age groups, from a physical examination database. Corresponding brain functional networks of the two groups were constructed by thresholding average cerebral glucose metabolism correlation matrices of 90 regions and analysed using graph theoretical approaches. Although both groups showed normal small-world architecture in the PET networks, increased clustering and decreased efficiency were found in older subjects, implying a degeneration process that brain system shifts from a small-world network to regular one along with normal aging. Moreover, normal senescence was related to changed nodal centralities predominantly in association and paralimbic cortex regions, e.g. increasing in orbitofrontal cortex (middle) and decreasing in left hippocampus. Additionally, the older networks were about equally as robust to random failures as younger counterpart, but more vulnerable against targeted attacks. Finally, methods in the construction of the PET networks revealed reasonable robustness. Our findings enhanced the understanding about the topological principles of PET networks and changes related to normal aging.

  20. Changes in Topological Organization of Functional PET Brain Network with Normal Aging

    PubMed Central

    Liu, Huafeng; Huang, Wenhua; Hu, Zhenghui

    2014-01-01

    Recent studies about brain network have suggested that normal aging is associated with alterations in coordinated patterns of the large-scale brain functional and structural systems. However, age-related changes in functional networks constructed via positron emission tomography (PET) data are still barely understood. Here, we constructed functional brain networks composed of regions in younger (mean age years) and older (mean age years) age groups with PET data. younger and older healthy individuals were separately selected for two age groups, from a physical examination database. Corresponding brain functional networks of the two groups were constructed by thresholding average cerebral glucose metabolism correlation matrices of regions and analysed using graph theoretical approaches. Although both groups showed normal small-world architecture in the PET networks, increased clustering and decreased efficiency were found in older subjects, implying a degeneration process that brain system shifts from a small-world network to regular one along with normal aging. Moreover, normal senescence was related to changed nodal centralities predominantly in association and paralimbic cortex regions, e.g. increasing in orbitofrontal cortex (middle) and decreasing in left hippocampus. Additionally, the older networks were about equally as robust to random failures as younger counterpart, but more vulnerable against targeted attacks. Finally, methods in the construction of the PET networks revealed reasonable robustness. Our findings enhanced the understanding about the topological principles of PET networks and changes related to normal aging. PMID:24586370

  1. Studying variability in human brain aging in a population-based German cohort—rationale and design of 1000BRAINS

    PubMed Central

    Caspers, Svenja; Moebus, Susanne; Lux, Silke; Pundt, Noreen; Schütz, Holger; Mühleisen, Thomas W.; Gras, Vincent; Eickhoff, Simon B.; Romanzetti, Sandro; Stöcker, Tony; Stirnberg, Rüdiger; Kirlangic, Mehmet E.; Minnerop, Martina; Pieperhoff, Peter; Mödder, Ulrich; Das, Samir; Evans, Alan C.; Jöckel, Karl-Heinz; Erbel, Raimund; Cichon, Sven; Nöthen, Markus M.; Sturma, Dieter; Bauer, Andreas; Jon Shah, N.; Zilles, Karl; Amunts, Katrin

    2014-01-01

    The ongoing 1000 brains study (1000BRAINS) is an epidemiological and neuroscientific investigation of structural and functional variability in the human brain during aging. The two recruitment sources are the 10-year follow-up cohort of the German Heinz Nixdorf Recall (HNR) Study, and the HNR MultiGeneration Study cohort, which comprises spouses and offspring of HNR subjects. The HNR is a longitudinal epidemiological investigation of cardiovascular risk factors, with a comprehensive collection of clinical, laboratory, socioeconomic, and environmental data from population-based subjects aged 45–75 years on inclusion. HNR subjects underwent detailed assessments in 2000, 2006, and 2011, and completed annual postal questionnaires on health status. 1000BRAINS accesses these HNR data and applies a separate protocol comprising: neuropsychological tests of attention, memory, executive functions and language; examination of motor skills; ratings of personality, life quality, mood and daily activities; analysis of laboratory and genetic data; and state-of-the-art magnetic resonance imaging (MRI, 3 Tesla) of the brain. The latter includes (i) 3D-T1- and 3D-T2-weighted scans for structural analyses and myelin mapping; (ii) three diffusion imaging sequences optimized for diffusion tensor imaging, high-angular resolution diffusion imaging for detailed fiber tracking and for diffusion kurtosis imaging; (iii) resting-state and task-based functional MRI; and (iv) fluid-attenuated inversion recovery and MR angiography for the detection of vascular lesions and the mapping of white matter lesions. The unique design of 1000BRAINS allows: (i) comprehensive investigation of various influences including genetics, environment and health status on variability in brain structure and function during aging; and (ii) identification of the impact of selected influencing factors on specific cognitive subsystems and their anatomical correlates. PMID:25071558

  2. The effects of physical activity, education, and body mass index on the aging brain.

    PubMed

    Ho, April J; Raji, Cyrus A; Becker, James T; Lopez, Oscar L; Kuller, Lewis H; Hua, Xue; Dinov, Ivo D; Stein, Jason L; Rosano, Caterina; Toga, Arthur W; Thompson, Paul M

    2011-09-01

    Normal human aging is accompanied by progressive brain tissue loss and cognitive decline; however, several factors are thought to influence brain aging. We applied tensor-based morphometry to high-resolution brain MRI scans to determine whether educational level or physical activity was associated with brain tissue volumes in the elderly, particularly in regions susceptible to age-related atrophy. We mapped the 3D profile of brain volume differences in 226 healthy elderly subjects (130F/96M; 77.9 ± 3.6 SD years) from the Cardiovascular Health Study-Cognition Study. Statistical maps revealed the 3D profile of brain regions whose volumes were associated with educational level and physical activity (based on leisure-time energy expenditure). After controlling for age, sex, and physical activity, higher educational levels were associated with ~2-3% greater tissue volumes, on average, in the temporal lobe gray matter. After controlling for age, sex, and education, greater physical activity was associated with ~2-2.5% greater average tissue volumes in the white matter of the corona radiata extending into the parietal-occipital junction. Body mass index (BMI) was highly correlated with both education and physical activity, so we examined BMI as a contributing factor by including physical activity, education, and BMI in the same model; only BMI effects remained significant. This is one of the largest MRI studies of factors influencing structural brain aging, and BMI may be a key factor explaining the observed relationship between education, physical activity, and brain structure. Independent contributions to brain structure could not be teased apart as all these factors were highly correlated with one another.

  3. PET Imaging of Tau Deposition in the Aging Human Brain

    PubMed Central

    Schonhaut, Daniel R.; O’Neil, James P.; Janabi, Mustafa; Ossenkoppele, Rik; Baker, Suzanne L.; Vogel, Jacob W.; Faria, Jamie; Schwimmer, Henry D.; Rabinovici, Gil D.; Jagust, William J.

    2016-01-01

    SUMMARY Tau pathology is a hallmark of Alzheimer’s disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent 18F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid, and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition. PMID:26938442

  4. Head impact accelerations for brain strain-related responses in contact sports: a model-based investigation.

    PubMed

    Ji, Songbai; Zhao, Wei; Li, Zhigang; McAllister, Thomas W

    2014-10-01

    Both linear [Formula: see text] and rotational [Formula: see text] accelerations contribute to head impacts on the field in contact sports; however, they are often isolated in injury studies. It is critical to evaluate the feasibility of estimating brain responses using isolated instead of full degrees-of-freedom (DOFs) accelerations. In this study, we investigated the sensitivities of regional brain strain-related responses to resultant [Formula: see text] and [Formula: see text] as well as the relative contributions of these acceleration components to the responses via random sampling and linear regression using parameterized, triangulated head impacts with kinematic variable values based on on-field measurements. Two independently established and validated finite element models of the human head were employed to evaluate model-consistency and dependency in results: the Dartmouth Head Injury Model and Simulated Injury Monitor. For the majority of the brain, volume-weighted regional peak strain, strain rate, and von Mises stress accumulated from the simulation significantly correlated with the product of the magnitude and duration of [Formula: see text], or effectively, the rotational velocity, but not to [Formula: see text]. Responses from [Formula: see text]-only were comparable to the full-DOF counterparts especially when normalized by injury-causing thresholds (e.g., volume fractions of large differences virtually diminished (i.e., [Formula: see text]1 %) at typical difference percentage levels of 1-4 % on average). These model-consistent results support the inclusion of both rotational acceleration magnitude and duration into kinematics-based injury metrics and demonstrate the feasibility of estimating strain-related responses from isolated [Formula: see text] for analyses of strain-induced injury relevant to contact sports without significant loss of accuracy, especially for the cerebrum.

  5. Microglia-aging: roles of microglial lysosome- and mitochondria-derived reactive oxygen species in brain aging.

    PubMed

    Nakanishi, Hiroshi; Wu, Zhou

    2009-07-19

    The accumulation of lysosome- and mitochondria-derived reactive oxygen species (ROS) are the most important causative factors for aging. Autophagic dysfunction and mitochondrial DNA damage in the central nervous system (CNS) are prominently found in microglia, the resident mononuclear phagocyte population within the CNS. The autophagic dysfunction may induce the defective turnover of mitochondria, which results in the accumulation of ROS-hypergenerating older mitochondria in microglia. ROS activate redox-dependent transduction cascades and transcription factors, including nuclear factor-kappaB, which induce the expression of inflammatory genes. Therefore, "microglia-aging" could function as a major driver for brain aging. Furthermore, the prevention of lysosomal autophagic dysfunction and mitochondrial DNA damage in microglia may therefore be a potentially effective new pharmaceutical intervention against brain aging.

  6. R2* mapping for brain iron: associations with cognition in normal aging.

    PubMed

    Ghadery, Christine; Pirpamer, Lukas; Hofer, Edith; Langkammer, Christian; Petrovic, Katja; Loitfelder, Marisa; Schwingenschuh, Petra; Seiler, Stephan; Duering, Marco; Jouvent, Eric; Schmidt, Helena; Fazekas, Franz; Mangin, Jean-Francois; Chabriat, Hugues; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

    2015-02-01

    Brain iron accumulates during aging and has been associated with neurodegenerative disorders including Alzheimer's disease. Magnetic resonance (MR)-based R2* mapping enables the in vivo detection of iron content in brain tissue. We investigated if during normal brain aging iron load relates to cognitive impairment in region-specific patterns in a community-dwelling cohort of 336 healthy, middle aged, and older adults from the Austrian Stroke Prevention Family Study. MR imaging and R2* mapping in the basal ganglia and neocortex were done at 3T. Comprehensive neuropsychological testing assessed memory, executive function, and psychomotor speed. We found the highest iron concentration in the globus pallidus, and pallidal and putaminal iron was significantly and inversely associated with cognitive performance in all cognitive domains, except memory. These associations were iron load dependent. Vascular brain lesions and brain volume did not mediate the relationship between iron and cognitive performance. We conclude that higher R2*-determined iron in the basal ganglia correlates with cognitive impairment during brain aging independent of concomitant brain abnormalities. The prognostic significance of this finding needs to be determined.

  7. Brain volumetric changes and cognitive ageing during the eighth decade of life.

    PubMed

    Ritchie, Stuart J; Dickie, David Alexander; Cox, Simon R; Valdes Hernandez, Maria Del C; Corley, Janie; Royle, Natalie A; Pattie, Alison; Aribisala, Benjamin S; Redmond, Paul; Muñoz Maniega, Susana; Taylor, Adele M; Sibbett, Ruth; Gow, Alan J; Starr, John M; Bastin, Mark E; Wardlaw, Joanna M; Deary, Ian J

    2015-12-01

    Later-life changes in brain tissue volumes--decreases in the volume of healthy grey and white matter and increases in the volume of white matter hyperintensities (WMH)--are strong candidates to explain some of the variation in ageing-related cognitive decline. We assessed fluid intelligence, memory, processing speed, and brain volumes (from structural MRI) at mean age 73 years, and at mean age 76 in a narrow-age sample of older individuals (n = 657 with brain volumetric data at the initial wave, n = 465 at follow-up). We used latent variable modeling to extract error-free cognitive levels and slopes. Initial levels of cognitive ability were predictive of subsequent brain tissue volume changes. Initial brain volumes were not predictive of subsequent cognitive changes. Brain volume changes, especially increases in WMH, were associated with declines in each of the cognitive abilities. All statistically significant results were modest in size (absolute r-values ranged from 0.114 to 0.334). These results build a comprehensive picture of macrostructural brain volume changes and declines in important cognitive faculties during the eighth decade of life.

  8. Probing astrocyte metabolism in vivo: proton magnetic resonance spectroscopy in the injured and aging brain

    PubMed Central

    Harris, Janna L.; Choi, In-Young; Brooks, William M.

    2015-01-01

    Following a brain injury, the mobilization of reactive astrocytes is part of a complex neuroinflammatory response that may have both harmful and beneficial effects. There is also evidence that astrocytes progressively accumulate in the normal aging brain, increasing in both number and size. These astrocyte changes in normal brain aging may, in the event of an injury, contribute to the exacerbated injury response and poorer outcomes observed in older traumatic brain injury (TBI) survivors. Here we present our view that proton magnetic resonance spectroscopy (1H-MRS), a neuroimaging approach that probes brain metabolism within a defined region of interest, is a promising technique that may provide insight into astrocyte metabolic changes in the injured and aging brain in vivo. Although 1H-MRS does not specifically differentiate between cell types, it quantifies certain metabolites that are highly enriched in astrocytes (e.g., Myo-inositol, mlns), or that are involved in metabolic shuttling between astrocytes and neurons (e.g., glutamate and glutamine). Here we focus on metabolites detectable by 1H-MRS that may serve as markers of astrocyte metabolic status. We review the physiological roles of these metabolites, discuss recent 1H-MRS findings in the injured and aging brain, and describe how an astrocyte metabolite profile approach might be useful in clinical medicine and clinical trials. PMID:26578948

  9. Exercise reduces activation of microglia isolated from hippocampus and brain of aged mice

    PubMed Central

    2013-01-01

    Background Aging is associated with low-grade neuroinflammation that includes basal increases in proinflammatory cytokines and expression of inflammatory markers on microglia. Exercise can reduce neuroinflammation following infection in aged animals, but whether exercise modulates basal changes in microglia activation is unknown. Therefore, we evaluated changes in basal microglia activation in cells isolated from the hippocampus and remaining brain following running-wheel access. Methods Adult (4 months) and aged (22 months) male and female BALB/c mice were housed with or without running wheels for 10 weeks. Microglia were isolated from the hippocampus or remaining brain. Flow cytometry was used to determine microglia (CD11b+ and CD45low) that co-labeled with CD86, CD206, and MHC II. Results Aged mice showed a greater proportion of CD86 and MHC II positive microglia. In aged females, access to a running wheel decreased proportion of CD86+ and MHC II+ microglia in the hippocampus whereas aged males in the running group showed a decrease in the proportion of CD86+ microglia in the brain and an increase in the proportion of MHC II+ microglia in hippocampus and brain. Conclusion Overall, these data indicate that running-wheel access modulates microglia activation, but these effects vary by age, sex, and brain region. PMID:24044641

  10. Gender differences in age effect on brain atrophy measured by magnetic resonance imaging

    SciTech Connect

    Gur, R.C.; Mozley, P.D.; Resnick.S.M.; Gottlieb, G.L.; Kohn, M.; Zimmerman, R.; Herman, G.; Atlas, S.; Grossman, R.; Berretta, D.; Erwin, R.; Gur, R.E. )

    1991-04-01

    A prospective sample of 69 healthy adults, age range 18-80 years, was studied with magnetic resonance imaging scans of the entire cranium. Volumes were obtained by a segmentation algorithm that uses proton density and T{sub 2} pixel values to correct field inhomogeneities (shading). Average ({plus minus}SD) brain volume, excluding cerebellum, was 1090.91 ml and cerebrospinal fluid (DSF) volume was 127.91 ml. Brain volume was higher (by 5 ml) in the right hemisphere. Men had 91 ml higher brain and 20 ml higher CSF volume than women. Age was negatively correlated with brain volume and positively correlated with CSF volume. The slope fo the regression line with age for CSF was steeper for men than women. This difference in slopes was significant for sulca but not ventricular, CSF. The greatest amount of atrophy in elderly men was in the left hemisphere, whereas is women age effects were symmetric. The findings may point to neuroanatomic substrates of hemispheric specialization and gender differences in age-related changes in brain function. They suggest that women are less vulnerable to age-related changes in mental abilities, whereas men are particularly susceptible to aging effects on left hemispheric functions.

  11. Accelerated aging of solid lubricants for the W76-1 TSL : effects of polymer outgassing.

    SciTech Connect

    Dugger, Michael Thomas; Wallace, William O.; Huffman, Elizabeth M.

    2006-09-01

    The behavior of MoS{sub 2} lubricants intended for the W76-1 TSL was evaluated after 17 and 82 thermal cycles, each lasting seven days and including a low temperature of -35 C and a high temperature of 93 C, in a sealed container containing organic materials. The MoS{sub 2} was applied by tumbling with MoS{sub 2} powder and steel pins (harperized), or by spraying with a resin binder (AS Mix). Surface composition measurements indicated an uptake of carbon and silicon on the lubricant surfaces after aging. Oxidation of the MoS{sub 2} on harperized coupons, where enough MoS{sub 2} was present at the surface to result in significant Mo and S concentrations, was found to be minimal for the thermal cycles in an atmosphere of primarily nitrogen. Bare steel surfaces showed a reduction in friction for exposed coupons compared to control coupons stored in nitrogen, at least for the initial cycles of sliding until the adsorbed contaminants were worn away. Lubricated surfaces showed no more than a ten percent increase in steady-state friction coefficient after exposure. Initial coefficient of friction was up to 250 percent higher than steady-state for AS Mix films on H950 coupons after 82 thermal cycles. However, the friction coefficient exhibited by lubricated coupons was never greater than 0.25, and more often less than 0.15, even after the accelerated aging exposures.

  12. The effect of accelerated ageing on performance properties of addition type silicone biomaterials.

    PubMed

    Stathi, K; Tarantili, P A; Polyzois, G

    2010-05-01

    The UV-protection provided to addition type silicone elastomers by various colorants, such as conventional dry earth pigments, as well as the so called "functional or reactive" pigments, was investigated. Moreover, the effect of a UV light absorber and a silica filler was also explored. Under the experimental parameters of this work, the exposure of silicone to UV radiation resulted in some changes of the IR absorbance, thermal decomposition after 400 degrees C, T(g) and tensile properties, whereas the storage modulus of samples was not affected. The obtained spectroscopic data, as well as the results of TGA and storage modulus, were interpreted by assuming that chain scission takes place during aging, whereas the improvement of tensile strength allows the hypothesis of a post-curing process, initiated by UV radiation. Therefore, the increase of T(g) could partly be due to the above reason and, furthermore, to the contribution of a rearrangement of chain fragments within the free volume of the elastomeric material. Regarding the evaluation of various coloring agents used in this work, the obtained results show that dry pigments are more sensitive to accelerated ageing conditions in comparison with functional liquid pigments. Moreover, the hydrophobic character of silicone matrix is enhanced, with the addition of this type pigments because of the vinyl functional silanes groups present in their chemical structure. Finally, it should be noted that the incorporation of silica nanofiller did not seem to prevent the silicone elastomer from degradation upon UV irradiation, but showed a significant reinforcing effect.

  13. Splicing-directed therapy in a new mouse model of human accelerated aging.

    PubMed

    Osorio, Fernando G; Navarro, Claire L; Cadiñanos, Juan; López-Mejía, Isabel C; Quirós, Pedro M; Bartoli, Catherine; Rivera, José; Tazi, Jamal; Guzmán, Gabriela; Varela, Ignacio; Depetris, Danielle; de Carlos, Félix; Cobo, Juan; Andrés, Vicente; De Sandre-Giovannoli, Annachiara; Freije, José M P; Lévy, Nicolas; López-Otín, Carlos

    2011-10-26

    Hutchinson-Gilford progeria syndrome (HGPS) is caused by a point mutation in the LMNA gene that activates a cryptic donor splice site and yields a truncated form of prelamin A called progerin. Small amounts of progerin are also produced during normal aging. Studies with mouse models of HGPS have allowed the recent development of the first therapeutic approaches for this disease. However, none of these earlier works have addressed the aberrant and pathogenic LMNA splicing observed in HGPS patients because of the lack of an appropriate mouse model. Here, we report a genetically modified mouse strain that carries the HGPS mutation. These mice accumulate progerin, present histological and transcriptional alterations characteristic of progeroid models, and phenocopy the main clinical manifestations of human HGPS, including shortened life span and bone and cardiovascular aberrations. Using this animal model, we have developed an antisense morpholino-based therapy that prevents the pathogenic Lmna splicing, markedly reducing the accumulation of progerin and its associated nuclear defects. Treatment of mutant mice with these morpholinos led to a marked amelioration of their progeroid phenotype and substantially extended their life span, supporting the effectiveness of antisense oligonucleotide-based therapies for treating human diseases of accelerated aging.

  14. Stability of ethyl glucuronide in hair reference materials after accelerated aging.

    PubMed

    Ammann, D; Becker, R; Nehls, I

    2015-12-01

    Two different hair reference materials, one produced from authentic hair displaying an ethyl glucuronide (EtG) content of about 25 pg/mg and one obtained by fortification of blank hair to an EtG level of 85 pg/mg were submitted to accelerated aging between 4 °C and 60 °C for periods between one and 24 months. Subsequently, the EtG content was determined in the aged samples and untreated reference samples stored at -22 °C under repeatability conditions following the so-called isochronous approach. The EtG content remained stable even at 40 °C for 24 months and at 60 °C over six months. This is in contrast to many organic analytes contained in trace concentrations in diverse matrices. A slight but significant increase of the recovered EtG in case of authentic hair samples having been exposed for 24 months between 4 °C and 60 °C may be due to a temperature-driven process that allows increased recoveries of the physiologically embedded EtG.

  15. Recent Developments in Understanding Brain Aging: Implications for Alzheimer’s Disease and Vascular Cognitive Impairment

    PubMed Central

    Deak, Ferenc; Freeman, Willard M.; Ungvari, Zoltan; Csiszar, Anna

    2016-01-01

    As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer’s disease. PMID:26590911

  16. Recent Developments in Understanding Brain Aging: Implications for Alzheimer's Disease and Vascular Cognitive Impairment.

    PubMed

    Deak, Ferenc; Freeman, Willard M; Ungvari, Zoltan; Csiszar, Anna; Sonntag, William E

    2016-01-01

    As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer's disease.

  17. Ageing and brain white matter structure in 3,513 UK Biobank participants

    PubMed Central

    Cox, Simon R.; Ritchie, Stuart J.; Tucker-Drob, Elliot M.; Liewald, David C.; Hagenaars, Saskia P.; Davies, Gail; Wardlaw, Joanna M.; Gale, Catharine R.; Bastin, Mark E.; Deary, Ian J.

    2016-01-01

    Quantifying the microstructural properties of the human brain's connections is necessary for understanding normal ageing and disease. Here we examine brain white matter magnetic resonance imaging (MRI) data in 3,513 generally healthy people aged 44.64–77.12 years from the UK Biobank. Using conventional water diffusion measures and newer, rarely studied indices from neurite orientation dispersion and density imaging, we document large age associations with white matter microstructure. Mean diffusivity is the most age-sensitive measure, with negative age associations strongest in the thalamic radiation and association fibres. White matter microstructure across brain tracts becomes increasingly correlated in older age. This may reflect an age-related aggregation of systemic detrimental effects. We report several other novel results, including age associations with hemisphere and sex, and comparative volumetric MRI analyses. Results from this unusually large, single-scanner sample provide one of the most extensive characterizations of age associations with major white matter tracts in the human brain. PMID:27976682

  18. Aging, neurodegenerative disease, and traumatic brain injury: the role of neuroimaging.

    PubMed

    Esopenko, Carrie; Levine, Brian

    2015-02-15

    Traumatic brain injury (TBI) is a highly prevalent condition with significant effects on cognition and behavior. While the acute and sub-acute effects of TBI recover over time, relatively little is known about the long-term effects of TBI in relation to neurodegenerative disease. This issue has recently garnered a great deal of attention due to publicity surrounding chronic traumatic encephalopathy (CTE) in professional athletes, although CTE is but one of several neurodegenerative disorders associated with a history of TBI. Here, we review the literative on neurodegenerative disorders linked to remote TBI. We also review the evidence for neuroimaging changes associated with unhealthy brain aging in the context of remote TBI. We conclude that neuroimaging biomarkers have significant potential to increase understanding of the mechanisms of unhealthy brain aging and neurodegeneration following TBI, with potential for identifying those at risk for unhealthy brain aging prior to the clinical manifestation of neurodegenerative disease.

  19. Systematic Analysis of Long Noncoding RNAs in the Senescence-accelerated Mouse Prone 8 Brain Using RNA Sequencing

    PubMed Central

    Zhang, Shuai; Qin, Chunxia; Cao, Guoqiong; Xin, Wenfeng; Feng, Chengqiang; Zhang, Wensheng

    2016-01-01

    Long noncoding RNAs (lncRNAs) may play an important role in Alzheimer's disease (AD) pathogenesis. However, despite considerable research in this area, the comprehensive and systematic understanding of lncRNAs in AD is still limited. The emergence of RNA sequencing provides a predictor and has incomparable advantage compared with other methods, including microarray. In this study, we identified lncRNAs in a 7-month-old mouse brain through deep RNA sequencing using the senescence-accelerated mouse prone 8 (SAMP8) and senescence-accelerated mouse resistant 1 (SAMR1) models. A total of 599,985,802 clean reads and 23,334 lncRNA transcripts were obtained. Then, we identified 97 significantly upregulated and 114 significantly downregulated lncRNA transcripts from all cases in SAMP8 mice relative to SAMR1 mice. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses revealed that these significantly dysregulated lncRNAs were involved in regulating the development of AD from various angles, such as nerve growth factor term (GO: 1990089), mitogen-activated protein kinase signaling pathway, and AD pathway. Furthermore, the most probable AD-associated lncRNAs were predicted and listed in detail. Our study provided the systematic dissection of lncRNA profiling in SAMP8 mouse brain and accelerated the development of lncRNA biomarkers in AD. These attracting biomarkers could provide significant insights into AD therapy in the future. PMID:27483026

  20. Age-dependent differential expression profile of a novel intergenic long noncoding RNA in rat brain.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2015-11-01

    Long noncoding RNAs (lncRNAs) are ≥200 nt long, abundant class of non-protein coding RNAs that are transcribed in complex, sense- and antisense patterns from the intergenic and intronic regions of mammalian genome. Mammalian central nervous system constitutes the largest repertoire of noncoding transcripts that are known to be expressed in developmentally regulated and cell-type specific manners. Although many lncRNAs, functioning in the brain development and diseases are known, none involved in brain aging has been reported so far. Here, we report involvement of a novel, repeat sequence (simple repeats and SINES)-containing, trans-spliced, long intergenic non-protein coding RNA (lincRNA), named as LINC-RBE (rat brain expressed transcript) involved in maturation and aging of mammalian brain. The LINC-RBE is strongly expressed in the rat brain and the upstream/downstream sequences of its DNA in the chromosome 5 contain binding sites for many cell growth, survival and development-specific transcriptional factors. Through RT-PCR and RNA in situ hybridization, LINC-RBE was found to be expressed in an age-dependent manner with significantly higher level of expression in the brain of adult (16 weeks) compared to both immature (4 weeks) and old (70 weeks) rats. Moreover, the expression pattern of the LINC-RBE showed distinct association with the specific neuro-anatomical regions, cell types and sub-cellular compartments of the rat brain in an age-related manner. Thus, its expression increased from immature stage to adulthood and declined further in old age. This is a first-time report of involvement of an intergenic repeat sequence-containing lncRNA in different regions of the rat brain in an age-dependent manner.

  1. Age-dependent differential expression profile of a novel intergenic long noncoding RNA in rat brain.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2015-12-01

    Long noncoding RNAs (lncRNAs) are ≥ 200 nt long, abundant class of non-protein coding RNAs that are transcribed in complex, sense- and antisense patterns from the intergenic and intronic regions of mammalian genome. Mammalian central nervous system constitutes the largest repertoire of noncoding transcripts that are known to be expressed in developmentally regulated and cell-type specific manners. Although many lncRNAs, functioning in the brain development and diseases are known, none involved in brain aging has been reported so far. Here, we report involvement of a novel, repeat sequence (simple repeats and SINES)-containing, trans-spliced, long intergenic non-protein coding RNA (lincRNA), named as LINC-RBE (rat brain expressed transcript) involved in maturation and aging of mammalian brain. The LINC-RBE is strongly expressed in the rat brain and the upstream/downstream sequences of its DNA in the chromosome 5 contain binding sites for many cell growth, survival and development-specific transcriptional factors. Through RT-PCR and RNA in situ hybridization, LINC-RBE was found to be expressed in an age-dependent manner with significantly higher level of expression in the brain of adult (16 week) compared to both immature (4 week) and old (70 week) rats. Moreover, the expression pattern of the LINC-RBE showed distinct association with the specific neuro-anatomical regions, cell types and sub-cellular compartments of the rat brain in an age-related manner. Thus, its expression increased from immature stage to adulthood and declined further in old age. This is a first-time report of involvement of an intergenic repeat sequence-containing lncRNA in different regions of the rat brain in an age-dependent manner.

  2. MRI-based brain atrophy rates in ADNI phase 2: acceleration and enrichment considerations for clinical trials.

    PubMed

    Hua, Xue; Ching, Christopher R K; Mezher, Adam; Gutman, Boris A; Hibar, Derrek P; Bhatt, Priya; Leow, Alex D; Jack, Clifford R; Bernstein, Matt A; Weiner, Michael W; Thompson, Paul M

    2016-01-01

    The goal of this work was to assess statistical power to detect treatment effects in Alzheimer's disease (AD) clinical trials using magnetic resonance imaging (MRI)-derived brain biomarkers. We used unbiased tensor-based morphometry (TBM) to analyze n = 5,738 scans, from Alzheimer's Disease Neuroimaging Initiative 2 participants scanned with both accelerated and nonaccelerated T1-weighted MRI at 3T. The study cohort included 198 healthy controls, 111 participants with significant memory complaint, 182 with early mild cognitive impairment (EMCI) and 177 late mild cognitive impairment (LMCI), and 155 AD patients, scanned at screening and 3, 6, 12, and 24 months. The statistical power to track brain change in TBM-based imaging biomarkers depends on the interscan interval, disease stage, and methods used to extract numerical summaries. To achieve reasonable sample size estimates for potential clinical trials, the minimal scan interval was 6 months for LMCI and AD and 12 months for EMCI. TBM-based imaging biomarkers were not sensitive to MRI scan acceleration, which gave results comparable with nonaccelerated sequences. ApoE status and baseline amyloid-beta positron emission tomography data improved statistical power. Among healthy, EMCI, and LMCI participants, sample size requirements were significantly lower in the amyloid+/ApoE4+ group than for the amyloid-/ApoE4- group. ApoE4 strongly predicted atrophy rates across brain regions most affected by AD, but the remaining 9 of the top 10 AD risk genes offered no added predictive value in this cohort.

  3. Possible acceleration of aging by adjuvant chemotherapy: a cause of early onset frailty?

    PubMed

    Maccormick, Ronald Eric

    2006-01-01

    Cancer chemotherapy has three main applications. It is curative for a small number of malignancies including childhood leukemia, Hodgkin's and non-Hodgkin's lymphoma, and germ cell malignancies. It has a palliative role for most metastatic epithelial malignancies. Finally, it has an adjuvant role in several types of resected epithelial malignancies particularly breast cancer. First successfully employed in the mid 1970s, adjuvant chemotherapy is associated with up to a 30% relative improvement in long-term overall survival in high risk breast cancer but demonstrates significantly less absolute improvement. Now that adjuvant chemotherapy is being used in lower risk disease, both the relative and absolute improvement in overall survival is even less impressive. With a growing number of long-term survivors, we are only now able to define the delayed implications of adjuvant chemotherapy. These long-term side effects include acceleration of neurocognitive decline, musculoskeletal complications such as early onset osteoporosis, premature skin and ocular changes and the most common long-term complaint; mild to profound fatigue. This complex of problems is suggestive of early onset frailty. This paper explores various potential mechanisms of aging including accumulation of free-radical damage, accumulation of DNA damage, telomere shortening with accompanying decline in telomerase activity and finally a decline in neuroendocrine/immune function. The impact of chemotherapy, particularly those agents used in the adjuvant setting, in relationship to these aging mechanisms is explored. There is good evidence that chemotherapy can effect all these aging mechanisms leading to early onset frailty. The implications of this hypothesis are quite profound. Whereas short-term toxicity of chemotherapy can usually be considered acceptable even for a small improvement in survival, long-term toxicity such as early onset frailty can have an impact on quality of life that could last for

  4. Cannabis exposure as an interactive cardiovascular risk factor and accelerant of organismal ageing: a longitudinal study

    PubMed Central

    Reece, Albert Stuart; Hulse, Gary Kenneth

    2016-01-01

    Objectives Many reports exist of the cardiovascular toxicity of smoked cannabis but none of arterial stiffness measures or vascular age (VA). In view of its diverse toxicology, the possibility that cannabis-exposed patients may be ageing more quickly requires investigation. Design Cross-sectional and longitudinal, observational. Prospective. Setting Single primary care addiction clinic in Brisbane, Australia. Participants 11 cannabis-only smokers, 504 tobacco-only smokers, 114 tobacco and cannabis smokers and 534 non-smokers. Exclusions: known cardiovascular disease or therapy or acute exposure to alcohol, amphetamine, heroin or methadone. Intervention Radial arterial pulse wave tonometry (AtCor, SphygmoCor, Sydney) performed opportunistically and sequentially on patients between 2006 and 2011. Main outcome measure Algorithmically calculated VA. Secondary outcomes: other central haemodynamic variables. Results Differences between group chronological ages (CA, 30.47±0.48 to 40.36±2.44, mean±SEM) were controlled with linear regression. Between-group sex differences were controlled by single-sex analysis. Mean cannabis exposure among patients was 37.67±7.16 g-years. In regression models controlling for CA, Body Mass Index (BMI), time and inhalant group, the effect of cannabis use on VA was significant in males (p=0.0156) and females (p=0.0084). The effect size in males was 11.84%. A dose–response relationship was demonstrated with lifetime exposure (p<0.002) additional to that of tobacco and opioids. In both sexes, the effect of cannabis was robust to adjustment and was unrelated to its acute effects. Significant power interactions between cannabis exposure and the square and cube of CA were demonstrated (from p<0.002). Conclusions Cannabis is an interactive cardiovascular risk factor (additional to tobacco and opioids), shows a prominent dose–response effect and is robust to adjustment. Cannabis use is associated with an acceleration of the cardiovascular

  5. Brain SERT Expression of Male Rats Is Reduced by Aging and Increased by Testosterone Restitution

    PubMed Central

    Herrera-Pérez, José Jaime; Fernández-Guasti, Alonso; Martínez-Mota, Lucía

    2013-01-01

    In preclinical and clinical studies aging has been associated with a deteriorated response to antidepressant treatment. We hypothesize that such impairment is explained by an age-related decrease in brain serotonin transporter (SERT) expression associated with low testosterone (T) levels. The objectives of this study were to establish (1) if brain SERT expression is reduced by aging and (2) if the SERT expression in middle-aged rats is increased by T-restitution. Intact young rats (3–5 months) and gonad-intact middle-aged rats with or without T-restitution were used. The identification of the brain SERT expression was done by immunofluorescence in prefrontal cortex, lateral septum, hippocampus, and raphe nuclei. An age-dependent reduction of SERT expression was observed in all brain regions examined, while T-restitution recovered the SERT expression only in the dorsal raphe of middle-aged rats. This last action seems relevant since dorsal raphe plays an important role in the antidepressant action of selective serotonin reuptake inhibitors. All data suggest that this mechanism accounts for the T-replacement usefulness to improve the response to antidepressants in the aged population. PMID:26317087

  6. The Ageing Brain: Effects on DNA Repair and DNA Methylation in Mice

    PubMed Central

    Langie, Sabine A. S.; Cameron, Kerry M.; Ficz, Gabriella; Oxley, David; Tomaszewski, Bartłomiej; Gorniak, Joanna P.; Maas, Lou M.; Godschalk, Roger W. L.; van Schooten, Frederik J.; Reik, Wolf; von Zglinicki, Thomas; Mathers, John C.

    2017-01-01

    Base excision repair (BER) may become less effective with ageing resulting in accumulation of DNA lesions, genome instability and altered gene expression that contribute to age-related degenerative diseases. The brain is particularly vulnerable to the accumulation of DNA lesions; hence, proper functioning of DNA repair mechanisms is important for neuronal survival. Although the mechanism of age-related decline in DNA repair capacity is unknown, growing evidence suggests that epigenetic events (e.g., DNA methylation) contribute to the ageing process and may be functionally important through the regulation of the expression of DNA repair genes. We hypothesize that epigenetic mechanisms are involved in mediating the age-related decline in BER in the brain. Brains from male mice were isolated at 3–32 months of age. Pyrosequencing analyses revealed significantly increased Ogg1 methylation with ageing, which correlated inversely with Ogg1 expression. The reduced Ogg1 expression correlated with enhanced expression of methyl-CpG binding protein 2 and ten-eleven translocation enzyme 2. A significant inverse correlation between Neil1 methylation at CpG-site2 and expression was also observed. BER activity was significantly reduced and associated with increased 8-oxo-7,8-dihydro-2′-deoxyguanosine levels. These data indicate that Ogg1 and Neil1 expression can be epigenetically regulated, which may mediate the effects of ageing on DNA repair in the brain. PMID:28218666

  7. GeneMining: identification, visualization, and interpretation of brain ageing signatures.

    PubMed

    Salle, Paola; Bringay, Sandra; Teisseire, Maguelonne; Chakkour, Feirouz; Roche, Mathieu; Rassoul, Ronza Abdel; Verdier, Jean-Michel; Devau, Gina

    2009-01-01

    Transcriptomic technologies are promising tools for identifying new genes involved in cerebral ageing or in neurodegenerative diseases such as Alzheimer's disease. These technologies produce massive biological data, which so far are extremely difficult to exploit. In this context, we propose GeneMining, a multidisciplinary methodology, which aims at developing new strategies to analyse such data, and to design interactive tools to help biologists to identify, visualize and interpret brain ageing signatures. In order to address the specific problem of brain ageing signatures discovery, we combine and apply existing tools with emphasis to a new efficient data mining method based on sequential patterns.

  8. Language in the aging brain: the network dynamics of cognitive decline and preservation.

    PubMed

    Shafto, Meredith A; Tyler, Lorraine K

    2014-10-31

    Language is a crucial and complex lifelong faculty, underpinned by dynamic interactions within and between specialized brain networks. Whereas normal aging impairs specific aspects of language production, most core language processes are robust to brain aging. We review recent behavioral and neuroimaging evidence showing that language systems remain largely stable across the life span and that both younger and older adults depend on dynamic neural responses to linguistic demands. Although some aspects of network dynamics change with age, there is no consistent evidence that core language processes are underpinned by different neural networks in younger and older adults.

  9. Brain-Skin Connection: Stress, Inflammation and Skin Aging

    PubMed Central

    Chen, Ying; Lyga, John

    2014-01-01

    The intricate relationship between stress and skin conditions has been documented since ancient times. Recent clinical observations also link psychological stress to the onset or aggravation of multiple skin diseases. However, the exact underlying mechanisms have only been studied and partially revealed in the past 20 years or so. In this review, the authors will discuss the recent discoveries in the field of “Brain-Skin Connection”, summarizing findings from the overlapping fields of psychology, endocrinology, skin neurobiology, skin inflammation, immunology, and pharmacology. PMID:24853682

  10. Graph theoretical analysis of sedation's effect on whole brain functional system in school-aged children.

    PubMed

    Wei, Zhen; Alcauter, Sarael; Jin, Ke; Peng, Zi-Wen; Gao, Wei

    2013-01-01

    The neurophysiological mechanism underlying sedation, especially in school-aged children, remains largely unknown. The recently emerged resting-state functional magnetic resonance imaging (rsfMRI) technique, capable of delineating brain's functional interaction pattern among distributed brain areas, proves to be a unique and powerful tool to study sedation-induced brain reorganization. Based on a relatively large school-aged children population (n=28, 10.3±2.6 years, range 7-15 years) and leveraging rsfMRI and graph theoretical analysis, this study aims to delineate sedation-induced changes in brain's information transferring property from a whole brain system perspective. Our results show a global deterioration in brain's efficiency properties (p=0.0085 and 0.0018, for global and local efficiency, respectively) with a locally graded distribution featuring significant disruptions of key consciousness-related regions. Moreover, our results also indicate a redistribution of brain's information-processing hubs characterized by a right and posterior shift as consistent with the reduced level of consciousness during sedation. Overall, our findings inform a sedation-induced functional reorganization pattern in school-aged children that greatly improve our understanding of sedation's effect in children and may potentially serve as reference for future sedation-related experimental studies and clinical applications.

  11. Traumatic brain injury (TBI) in older adults: aging with a TBI versus incident TBI in the aged.

    PubMed

    Peters, Matthew E

    2016-12-01

    Approximately 39 million older adults (age >65) were evaluated for traumatic brain injury (TBI) in United States emergency departments during the 2-year period from 2009 to 2010, representing a 61% increase in estimates from prior years (Albrecht et al., 2015a). Across the lifespan, an estimated 5.3 million Americans are living with a TBI-related disability (Centers for Disease Control and Prevention (CDC), 2003). With improved recognition and management, more individuals experiencing TBI are surviving to die of other causes later in life (Flanagan et al., 2005). Taken together, these statistics highlight two important populations: those who are "aging with a TBI" and "incident TBI in the aged."

  12. Correlations among brain gray matter volumes, age, gender, and hemisphere in healthy individuals.

    PubMed

    Taki, Yasuyuki; Thyreau, Benjamin; Kinomura, Shigeo; Sato, Kazunori; Goto, Ryoi; Kawashima, Ryuta; Fukuda, Hiroshi

    2011-01-01

    To determine the relationship between age and gray matter structure and how interactions between gender and hemisphere impact this relationship, we examined correlations between global or regional gray matter volume and age, including interactions of gender and hemisphere, using a general linear model with voxel-based and region-of-interest analyses. Brain magnetic resonance images were collected from 1460 healthy individuals aged 20-69 years; the images were linearly normalized and segmented and restored to native space for analysis of global gray matter volume. Linearly normalized images were then non-linearly normalized and smoothed for analysis of regional gray matter volume. Analysis of global gray matter volume revealed a significant negative correlation between gray matter ratio (gray matter volume divided by intracranial volume) and age in both genders, and a significant interaction effect of age × gender on the gray matter ratio. In analyzing regional gray matter volume, the gray matter volume of all regions showed significant main effects of age, and most regions, with the exception of several including the inferior parietal lobule, showed a significant age × gender interaction. Additionally, the inferior temporal gyrus showed a significant age × gender × hemisphere interaction. No regional volumes showed significant age × hemisphere interactions. Our study may contribute to clarifying the mechanism(s) of normal brain aging in each brain region.

  13. Differences between chronological and brain age are related to education and self-reported physical activity.

    PubMed

    Steffener, Jason; Habeck, Christian; O'Shea, Deirdre; Razlighi, Qolamreza; Bherer, Louis; Stern, Yaakov

    2016-04-01

    This study investigated the relationship between education and physical activity and the difference between a physiological prediction of age and chronological age (CA). Cortical and subcortical gray matter regional volumes were calculated from 331 healthy adults (range: 19-79 years). Multivariate analyses identified a covariance pattern of brain volumes best predicting CA (R(2) = 47%). Individual expression of this brain pattern served as a physiologic measure of brain age (BA). The difference between CA and BA was predicted by education and self-report measures of physical activity. Education and the daily number of flights of stairs climbed (FOSC) were the only 2 significant predictors of decreased BA. Effect sizes demonstrated that BA decreased by 0.95 years for each year of education and by 0.58 years for 1 additional FOSC daily. Effects of education and FOSC on regional brain volume were largely driven by temporal and subcortical volumes. These results demonstrate that higher levels of education and daily FOSC are related to larger brain volume than predicted by CA which supports the utility of regional gray matter volume as a biomarker of healthy brain aging.

  14. Age at First Episode Modulates Diagnosis-Related Structural Brain Abnormalities in Psychosis

    PubMed Central

    Pina-Camacho, Laura; Del Rey-Mejías, Ángel; Janssen, Joost; Bioque, Miquel; González-Pinto, Ana; Arango, Celso; Lobo, Antonio; Sarró, Salvador; Desco, Manuel; Sanjuan, Julio; Lacalle-Aurioles, Maria; Cuesta, Manuel J.; Saiz-Ruiz, Jerónimo; Bernardo, Miguel; Parellada, Mara

    2016-01-01

    Brain volume and thickness abnormalities have been reported in first-episode psychosis (FEP). However, it is unclear if and how they are modulated by brain developmental stage (and, therefore, by age at FEP as a proxy). This is a multicenter cross-sectional case-control brain magnetic resonance imaging (MRI) study. Patients with FEP (n = 196), 65.3% males, with a wide age at FEP span (12–35 y), and healthy controls (HC) (n = 157), matched for age, sex, and handedness, were scanned at 6 sites. Gray matter volume and thickness measurements were generated for several brain regions using FreeSurfer software. The nonlinear relationship between age at scan (a proxy for age at FEP in patients) and volume and thickness measurements was explored in patients with schizophrenia spectrum disorders (SSD), affective psychoses (AFP), and HC. Earlier SSD cases (ie, FEP before 15–20 y) showed significant volume and thickness deficits in frontal lobe, volume deficits in temporal lobe, and volume enlargements in ventricular system and basal ganglia. First-episode AFP patients had smaller cingulate cortex volume and thicker temporal cortex only at early age at FEP (before 18–20 y). The AFP group also had age-constant (12–35-y age span) volume enlargements in the frontal and parietal lobe. Our study suggests that age at first episode modulates the structural brain abnormalities found in FEP patients in a nonlinear and diagnosis-dependent manner. Future MRI studies should take these results into account when interpreting samples with different ages at onset and diagnosis. PMID:26371339

  15. Upregulation of Aβ42 in the Brain and Bodily Fluids of Rhesus Monkeys with Aging.

    PubMed

    Zhao, Qiao; Lu, Jing; Yao, Zitong; Wang, Shubo; Zhu, Liming; Wang, Ju; Chen, Baian

    2017-01-01

    The cerebral accumulation of amyloid beta (Aβ) is one of the key pathological hallmarks of Alzheimer's disease (AD). Aβ is also found in bodily fluids such as the cerebrospinal fluid (CSF) and plasma. However, the significance of Aβ accumulation in the brain and different bodily pools, as well as its correlation with aging and cerebral amyloid pathology, is not completely understood. To better understand this question, we selected the rhesus monkey, which is phylogenetically and physiologically highly similar to the human, as a model to study. We quantified the levels of the two main Aβ isoforms (Aβ42 and Aβ40) in different sections of the brain (frontal cortex, temporal cortex, and hippocampus) and bodily fluids (CSF and plasma) of rhesus monkeys at different developmental phases (young, 5-9 years of age; mature, 10-19 years of age; and old, 21-24 years of age). We found that the levels of neuronal and insoluble Aβ42 increased significantly in the brain with aging, suggesting that this specific isoform might be directly involved in aging and AD-like pathophysiology. There was no significant change in the Aβ40 level in the brain with aging. In addition, the Aβ42 level, but not the Aβ40 level, in both the CSF and plasma increased with aging. We also identified a positive correlation between Aβ42 in the CSF and plasma and Aβ42 in the brain. Taken collectively, our results indicate that there is an association between Aβ accumulation and age. These results support the increased incidence of AD with aging.

  16. Stochastic fluctuations in gene expression in aging hippocampal neurons could be exacerbated by traumatic brain injury.

    PubMed

    Shearer, Joseph; Boone, Deborah; Weisz, Harris; Jennings, Kristofer; Uchida, Tatsuo; Parsley, Margaret; DeWitt, Douglas; Prough, Donald; Hellmich, Helen

    2016-04-01

    Traumatic brain injury (TBI) is a risk factor for age-related dementia and development of neurodegenerative disorders such as Alzheimer's disease that are associated with cognitive decline. The exact mechanism for this risk is unknown but we hypothesized that TBI is exacerbating age-related changes in gene expression. Here, we present evidence in an animal model that experimental TBI increases age-related stochastic gene expression. We compared the variability in expression of several genes associated with cell survival or death, among three groups of laser capture microdissected hippocampal neurons from aging rat brains. TBI increased stochastic fluctuations in gene expression in both dying and surviving neurons compared to the naïve neurons. Increases in random, stochastic fluctuations in prosurvival or prodeath gene expression could potentially alter cell survival or cell death pathways in aging neurons after TBI which may lead to age-related cognitive decline.

  17. Exercise enhances memory consolidation in the aging brain.

    PubMed

    Snigdha, Shikha; de Rivera, Christina; Milgram, Norton W; Cotman, Carl W

    2014-01-01

    Exercise has been shown to reduce age-related losses in cognitive function including learning and memory, but the mechanisms underlying this effect remain poorly understood. Memory formation occurs in stages that include an initial acquisition phase, an intermediate labile phase, and then a process of consolidation which leads to long-term memory formation. An effective way to examine the mechanism by which exercise improves memory is to introduce the intervention (exercise), post-acquisition, making it possible to selectively examine memory storage and consolidation. Accordingly we evaluated the effects of post-trial exercise (10 min on a treadmill) on memory consolidation in aged canines both right after, an hour after, and 24 h after acute exercise training in concurrent discrimination, object location memory (OLM), and novel object recognition tasks. Our study shows that post-trial exercise facilitates memory function by improving memory consolidation in aged animals in a time-dependent manner. The improvements were significant at 24 h post-exercise and not right after or 1 h after exercise. Aged animals were also tested following chronic exercise (10 min/day for 14 consecutive days) on OLM or till criterion were reached (for reversal learning task). We found improvements from a chronic exercise design in both the object location and reversal learning tasks. Our studies suggest that mechanisms to improve overall consolidation and cognitive function remain accessible even with progressing age and can be re-engaged by both acute and chronic exercise.

  18. Altered prion protein glycosylation in the aging mouse brain.

    PubMed

    Goh, Angeline Xi-Hua; Li, Chaoyang; Sy, Man-Sun; Wong, Boon-Seng

    2007-02-01

    The normal cellular prion protein (PrP(C)) is a glycoprotein with two highly conserved potential N-linked glycosylation sites. All prion diseases, whether inherited, infectious or sporadic, are believed to share the same pathogenic mechanism that is based on the conversion of the normal cellular prion protein (PrP(C)) to the pathogenic scrapie prion protein (PrP(Sc)). However, the clinical and histopathological presentations of prion diseases are heterogeneous, depending not only on the strains of PrP(Sc) but also on the mechanism of diseases, such as age-related sporadic vs. infectious prion diseases. Accumulated evidence suggests that N-linked glycans on PrP(C) are important in disease phenotype. A better understanding of the nature of the N-linked glycans on PrP(C) during the normal aging process may provide new insights into the roles that N-linked glycans play in the pathogenesis of prion diseases. By using a panel of 19 lectins in an antibody-lectin enzyme-linked immunosorbent assay (ELISA), we found that the lectin binding profiles of PrP(C) alter significantly during aging. There is an increasing prevalence of complex oligosaccharides on the aging PrP(C), which are features of PrP(Sc). Taken together, this study suggests a link between the glycosylation patterns on PrP(C) during aging and PrP(Sc).

  19. Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

    PubMed

    Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

    2014-01-01

    Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections

  20. Hippocampal Astrocyte Cultures from Adult and Aged Rats Reproduce Changes in Glial Functionality Observed in the Aging Brain.

    PubMed

    Bellaver, Bruna; Souza, Débora Guerini; Souza, Diogo Onofre; Quincozes-Santos, André

    2016-03-30

    Astrocytes are dynamic cells that maintain brain homeostasis, regulate neurotransmitter systems, and process synaptic information, energy metabolism, antioxidant defenses, and inflammatory response. Aging is a biological process that is closely associated with hippocampal astrocyte dysfunction. In this sense, we demonstrated that hippocampal astrocytes from adult and aged Wistar rats reproduce the glial functionality alterations observed in aging by evaluating several senescence, glutamatergic, oxidative and inflammatory parameters commonly associated with the aging process. Here, we show that the p21 senescence-associated gene and classical astrocyte markers, such as glial fibrillary acidic protein (GFAP), vimentin, and actin, changed their expressions in adult and aged astrocytes. Age-dependent changes were also observed in glutamate transporters (glutamate aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1)) and glutamine synthetase immunolabeling and activity. Additionally, according to in vivo aging, astrocytes from adult and aged rats showed an increase in oxidative/nitrosative stress with mitochondrial dysfunction, an increase in RNA oxidation, NADPH oxidase (NOX) activity, superoxide levels, and inducible nitric oxide synthase (iNOS) expression levels. Changes in antioxidant defenses were also observed. Hippocampal astrocytes also displayed age-dependent inflammatory response with augmentation of proinflammatory cytokine levels, such as TNF-α, IL-1β, IL-6, IL-18, and messenger RNA (mRNA) levels of cyclo-oxygenase 2 (COX-2). Furthermore, these cells secrete neurotrophic factors, including glia-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), S100 calcium-binding protein B (S100B) protein, and transforming growth factor-β (TGF-β), which changed in an age-dependent manner. Classical signaling pathways associated with aging, such as nuclear factor erythroid-derived 2-like 2 (Nrf2), nuclear factor kappa B (NFκ

  1. Brain plasticity and functional losses in the aged: scientific bases for a novel intervention.

    PubMed

    Mahncke, Henry W; Bronstone, Amy; Merzenich, Michael M

    2006-01-01

    Aging is associated with progressive losses in function across multiple systems, including sensation, cognition, memory, motor control, and affect. The traditional view has been that functional decline in aging is unavoidable because it is a direct consequence of brain machinery wearing down over time. In recent years, an alternative perspective has emerged, which elaborates on this traditional view of age-related functional decline. This new viewpoint--based upon decades of research in neuroscience, experimental psychology, and other related fields--argues that as people age, brain plasticity processes with negative consequences begin to dominate brain functioning. Four core factors--reduced schedules of brain activity, noisy processing, weakened neuromodulatory control, and negative learning--interact to create a self-reinforcing downward spiral of degraded brain function in older adults. This downward spiral might begin from reduced brain activity due to behavioral change, from a loss in brain function driven by aging brain machinery, or more likely from both. In aggregate, these interrelated factors promote plastic changes in the brain that result in age-related functional decline. This new viewpoint on the root causes of functional decline immediately suggests a remedial approach. Studies of adult brain plasticity have shown that substantial improvement in function and/or recovery from losses in sensation, cognition, memory, motor control, and affect should be possible, using appropriately designed behavioral training paradigms. Driving brain plasticity with positive outcomes requires engaging older adults in demanding sensory, cognitive, and motor activities on an intensive basis, in a behavioral context designed to re-engage and strengthen the neuromodulatory systems that control learning in adults, with the goal of increasing the fidelity, reliability, and power of cortical representations. Such a training program would serve a substantial unmet need in

  2. [Autonomic regulation at emotional stress under hypoxic conditions in the elderly with physiological and accelerated aging: effect of hypoxic training].

    PubMed

    Os'mak, E D; Asanov, É O

    2014-01-01

    The effect of hypoxic training on autonomic regulation in psycho-emotional stress conditions in hypoxic conditions in older people with physiological (25 people) and accelerated (28 people) aging respiratory system. It is shown that hypoxic training leads to an increase in vagal activity indicators (HF) and reduced simpatovagal index (LF/HF), have a normalizing effect on the autonomic balance during stress loads in older people with different types of aging respiratory system.

  3. Dissecting mechanisms of brain aging by studying the intrinsic excitability of neurons

    PubMed Central

    Rizzo, Valerio; Richman, Jeffrey; Puthanveettil, Sathyanarayanan V.

    2015-01-01

    Several studies using vertebrate and invertebrate animal models have shown aging associated changes in brain function. Importantly, changes in soma size, loss or regression of dendrites and dendritic spines and alterations in the expression of neurotransmitter receptors in specific neurons were described. Despite this understanding, how aging impacts intrinsic properties of individual neurons or circuits that govern a defined behavior is yet to be determined. Here we discuss current understanding of specific electrophysiological changes in individual neurons and circuits during aging. PMID:25610394

  4. Effect of aging on brain respiration and carbohydrate metabolism of Syrian hamsters.

    PubMed

    Fox, J H; Parmacek, M S; Patel-Mandlik, K

    1975-01-01

    Syrian hamsters were used to study the effect of aging on brain slice respiration and metabolism. Young animals (average age 8 months) and old animals (average age 18 months) were incubated under standard conditions with the following parameters being measured: oxygen uptake, 14CO2 production, glucose utilization, lactate and pyruvate formation. No differences were found in the two groups. It is still very likely that subtle differences exist but can only be documented under conditions of metabolic stress.

  5. Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging.

    PubMed

    Voss, Michelle W; Weng, Timothy B; Burzynska, Agnieszka Z; Wong, Chelsea N; Cooke, Gillian E; Clark, Rachel; Fanning, Jason; Awick, Elizabeth; Gothe, Neha P; Olson, Erin A; McAuley, Edward; Kramer, Arthur F

    2016-05-01

    Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the default mode network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks.

  6. Effect of Accelerated Artificial Aging on Translucency of Methacrylate and Silorane-Based Composite Resins

    PubMed Central

    Shirinzad, Mehdi; Rezaei-Soufi, Loghman; Mirtorabi, Maryam Sadat; Vahdatinia, Farshid

    2016-01-01

    Objectives: Composite restorations must have tooth-like optical properties namely color and translucency and maintain them for a long time. This study aimed to compare the effect of accelerated artificial aging (AAA) on the translucency of three methacrylate-based composites (Filtek Z250, Filtek Z250XT and Filtek Z350XT) and one silorane-based composite resin (Filtek P90). Materials and Methods: For this in vitro study, 56 composite discs were fabricated (n=14 for each group). Using scanning spectrophotometer, CIE L*a*b* parameters and translucency of each specimen were measured at 24 hours and after AAA for 384 hours. Data were analyzed using one-way ANOVA, Tukey's test and paired t-test at P=0.05 level of significance. Results: The mean (±standard deviation) translucency parameter for Filtek Z250, Filtek Z250XT, Filtek Z350XT and Filtek P90 was 5.67±0.64, 4.59±0.77, 7.87±0.82 and 4.21±0.71 before AAA and 4.25±0.615, 3.53±0.73, 5.94±0.57 and 4.12±0.54 after AAA, respectively. After aging, the translucency of methacrylate-based composites decreased significantly (P<0.05). However, the translucency of Filtek P90 did not change significantly (P>0.05). Conclusions: The AAA significantly decreased the translucency of methacrylate-based composites (Filtek Z250, Filtek Z250XT and Filtek Z350XT) but no change occurred in the translucency of Filtek P90 silorane-based composite. PMID:27928237

  7. Microstructure and mechanical properties of composite resins subjected to accelerated artificial aging.

    PubMed

    dos Reis, Andréa Cândido; de Castro, Denise Tornavoi; Schiavon, Marco Antônio; da Silva, Leandro Jardel; Agnelli, José Augusto Marcondes

    2013-01-01

    The aim of this study was to investigate the influence of accelerated artificial aging (AAA) on the microstructure and mechanical properties of the Filtek Z250, Filtek Supreme, 4 Seasons, Herculite, P60, Tetric Ceram, Charisma and Filtek Z100. composite resins. The composites were characterized by Fourier-transform Infrared spectroscopy (FTIR) and thermal analyses (Differential Scanning Calorimetry - DSC and Thermogravimetry - TG). The microstructure of the materials was examined by scanning electron microscopy. Surface hardness and compressive strength data of the resins were recorded and the mean values were analyzed statistically by ANOVA and Tukey's test (α=0.05). The results showed significant differences among the commercial brands for surface hardness (F=86.74, p<0.0001) and compressive strength (F=40.31, p<0.0001), but AAA did not affect the properties (surface hardness: F=0.39, p=0.53; compressive strength: F=2.82, p=0.09) of any of the composite resins. FTIR, DSC and TG analyses showed that resin polymerization was complete, and there were no differences between the spectra and thermal curve profiles of the materials obtained before and after AAA. TG confirmed the absence of volatile compounds and evidenced good thermal stability up to 200 °C, and similar amounts of residues were found in all resins evaluated before and after AAA. The AAA treatment did not significantly affect resin surface. Therefore, regardless of the resin brand, AAA did not influence the microstructure or the mechanical properties.

  8. Degradation mechanism of LiCoO2/mesocarbon microbeads battery based on accelerated aging tests

    NASA Astrophysics Data System (ADS)

    Guan, Ting; Zuo, Pengjian; Sun, Shun; Du, Chunyu; Zhang, Lingling; Cui, Yingzhi; Yang, Lijie; Gao, Yunzhi; Yin, Geping; Wang, Fuping

    2014-12-01

    A series of LiCoO2/mesocarbon microbeads (MCMB) commercial cells cycled at different rates (0.6C, 1.2C, 1.5C, 1.8C, 2.4C and 3.0C) are disassembled and the capacity fade mechanism is proposed by analyzing the structure, morphology and electrochemical performance evolution at the capacity retention of 95%, 90%, 85%, 80%. The capacity deterioration of the commercial cell is mainly caused by the decay of the reversible capacity of LiCoO2 cathode, the irreversible loss of active lithium and the lithium remaining in anode. The proportions of effects by the above three factors are calculated accurately. The consumption of the active lithium leads to a cell imbalance between the anode and the cathode. The electrochemical test results indicate that the capacity fade of the active materials at the low rate is more obvious than that at the high rate. The influence of the active lithium is gradually increscent with the increasing rate. The rate of 1.5C is the optimal value to accelerate the aging of the full cell by comparing the testing results at different capacity retentions in the specific condition of low charge/discharge rate and shallow depth of discharge.

  9. Coffee Silverskin Extract Protects against Accelerated Aging Caused by Oxidative Agents.

    PubMed

    Iriondo-DeHond, Amaia; Martorell, Patricia; Genovés, Salvador; Ramón, Daniel; Stamatakis, Konstantinos; Fresno, Manuel; Molina, Antonio; Del Castillo, Maria Dolores

    2016-06-01

    Nowadays, coffee beans are almost exclusively used for the preparation of the beverage. The sustainability of coffee production can be achieved introducing new applications for the valorization of coffee by-products. Coffee silverskin is the by-product generated during roasting, and because of its powerful antioxidant capacity, coffee silverskin aqueous extract (CSE) may be used for other applications, such as antiaging cosmetics and dermaceutics. This study aims to contribute to the coffee sector's sustainability through the application of CSE to preserve skin health. Preclinical data regarding the antiaging properties of CSE employing human keratinocytes and Caenorhabditis elegans are collected during the present study. Accelerated aging was induced by tert-butyl hydroperoxide (t-BOOH) in HaCaT cells and by ultraviolet radiation C (UVC) in C. elegans. Results suggest that the tested concentrations of coffee extracts were not cytotoxic, and CSE 1 mg/mL gave resistance to skin cells when oxidative damage was induced by t-BOOH. On the other hand, nematodes treated with CSE (1 mg/mL) showed a significant increased longevity compared to those cultured on a standard diet. In conclusion, our results support the antiaging properties of the CSE and its great potential for improving skin health due to its antioxidant character associated with phenols among other bioactive compounds present in the botanical material.

  10. Accelerated Aging Experiments for Prognostics of Damage Growth in Composite Materials

    NASA Technical Reports Server (NTRS)

    Saxena, Abhinav; Goebel, Kai Frank; Larrosa, Cecilia C.; Janapati, Vishnuvardhan; Roy, Surajit; Chang, Fu-Kuo

    2011-01-01

    Composite structures are gaining importance for use in the aerospace industry. Compared to metallic structures their behavior is less well understood. This lack of understanding may pose constraints on their use. One possible way to deal with some of the risks associated with potential failure is to perform in-situ monitoring to detect precursors of failures. Prognostic algorithms can be used to predict impending failures. They require large amounts of training data to build and tune damage model for making useful predictions. One of the key aspects is to get confirmatory feedback from data as damage progresses. These kinds of data are rarely available from actual systems. The next possible resource to collect such data is an accelerated aging platform. To that end this paper describes a fatigue cycling experiment with the goal to stress carbon-carbon composite coupons with various layups. Piezoelectric disc sensors were used to periodically interrogate the system. Analysis showed distinct differences in the signatures of growing failures between data collected at conditions. Periodic X-radiographs were taken to assess the damage ground truth. Results after signal processing showed clear trends of damage growth that were correlated to damage assessed from the X-ray images.

  11. Effect of Accelerated Aging on Color Change of Direct and Indirect Fiber-Reinforced Composite Restorations

    PubMed Central

    Tabatabaei, Masoumeh Hasani; Farahat, Farnaz; Ahmadi, Elham; Hassani, Zahra

    2016-01-01

    Objectives: The aim of this study was to assess the effect of artificial accelerated aging (AAA) on color change of direct and indirect fiber-reinforced composite (FRC) restorations. Materials and Methods: Direct (Z250) and indirect (Gradia) composite resins were reinforced with glass (GF) and polyethylene fibers (PF) based on the manufacturers’ instructions. Forty samples were fabricated and divided into eight groups (n=5). Four groups served as experimental groups and the remaining four served as controls. Color change (ΔE) and color parameters (ΔL*, Δa*, Δb*) were read at baseline and after AAA based on the CIELAB system. Three-way ANOVA and Tukey’s test were used for statistical analysis. Results: Significant differences were found in ΔE, ΔL*, Δa* and Δb* among the groups after AAA (P<0.05). Most of the studied samples demonstrated an increase in lightness and a red-yellow shift after AAA. Conclusions: The obtained ΔE values were unacceptable after AAA (ΔE≥ 3.3). All indirect samples showed a green-blue shift with a reduction in lightness except for Gradia/PF+ NuliteF. PMID:28392813

  12. Exceptional Brain Aging in a Rural Population-Based Cohort

    ERIC Educational Resources Information Center

    Kaye, Jeffrey; Michael, Yvonne; Calvert, James; Leahy, Marjorie; Crawford, Debbie; Kramer, Patricia

    2009-01-01

    Context: The 2000 US Census identified 50,454 Americans over the age of 100. Increased longevity is only of benefit if accompanied by maintenance of independence and quality of life. Little is known about the prevalence of dementia and other disabling conditions among rural centenarians although this information is important to clinicians caring…

  13. Grape juice, berries and walnuts affect brain aging and behavior

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous studies have indicated that individuals consuming a diet containing high amounts of fruits and vegetables exhibit fewer age-related diseases such as Alzheimer Disease (AD). A recent report has indicated that individuals who consumed a diet containing 2.5 servings of fruit and vegetables/day...

  14. Improving brain signaling in aging: could berries be the answer?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As the lifespan of humans is increasing, the quest for “healthy aging” is increasingly becoming a focus of the media and people. This trend is important, as the population of people over 65 years of age worldwide is expected to triple by midcentury. Many regard “healthy aging” as preventing wrinkles...

  15. Role of walnuts in maintaining brain health with age

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Due to the combination of population growth and population aging, increases in the incidence of chronic neurodegenerative disorders have become a societal concern, both in terms of decreased quality of life and increased financial burden. Clinical manifestation of many of these disorders takes years...

  16. Age-related epigenetic regulation in the brain and its role in neuronal diseases

    PubMed Central

    Kim-Ha, Jeongsil; Kim, Young-Joon

    2016-01-01

    Accumulating evidence indicates many brain functions are mediated by epigenetic regulation of neural genes, and their dysregulations result in neuronal disorders. Experiences such as learning and recall, as well as physical exercise, induce neuronal activation through epigenetic modifications and by changing the noncoding RNA profiles. Animal models, brain samples from patients, and the development of diverse analytical methods have broadened our understanding of epigenetic regulation in the brain. Diverse and specific epigenetic changes are suggested to correlate with neuronal development, learning and memory, aging and age-related neuronal diseases. Although the results show some discrepancies, a careful comparison of the data (including methods, regions and conditions examined) would clarify the problems confronted in understanding epigenetic regulation in the brain. PMID:27866512

  17. Hot Topics in Research: Preventive Neuroradiology in Brain Aging and Cognitive Decline.

    PubMed

    Raji, C A; Eyre, H; Wei, S H; Bredesen, D E; Moylan, S; Law, M; Small, G; Thompson, P M; Friedlander, R M; Silverman, D H; Baune, B T; Hoang, T A; Salamon, N; Toga, A W; Vernooij, M W

    2015-10-01

    Preventive neuroradiology is a new concept supported by growing literature. The main rationale of preventive neuroradiology is the application of multimodal brain imaging toward early and subclinical detection of brain disease and subsequent preventive actions through identification of modifiable risk factors. An insightful example of this is in the area of age-related cognitive decline, mild cognitive impairment, and dementia with potentially modifiable risk factors such as obesity, diet, sleep, hypertension, diabetes, depression, supplementation, smoking, and physical activity. In studying this link between lifestyle and cognitive decline, brain imaging markers may be instrumental as quantitative measures or even indicators of early disease. The purpose of this article is to provide an overview of the major studies reflecting how lifestyle factors affect the brain and cognition aging. In this hot topics review, we will specifically focus on obesity and physical activity.

  18. Effect of dietary, social, and lifestyle determinants of accelerated aging and its common clinical presentation: A survey study

    PubMed Central

    Samarakoon, S. M. S.; Chandola, H M; Ravishankar, B.

    2011-01-01

    Aging is unavoidable and natural phenomenon of life. Modern gerontologists are realizing the fact that aging is a disease, which Ayurveda had accepted as natural disease since long. Rate of aging is determined by one's biological, social, lifestyle, and psychological conditions and adversity of which leads to accelerated form of aging (Akalaja jara or premature aging). The aim of this study is to identify potential factors that may accelerate aging in the context of dietry factors, lifestyle and mental makeup. The 120 diagnosed subjects of premature-ageing of 30-60 years were randomly selected in the survey study. Premature ageing was common among females (75.83%), in 30-40 age group (70%), 86.67% were married, had secondary level of education (36.66%), house-views (61.67%), belongs top middle class (58.33%) and engaged in occupations that dominating physical labour (88.33%). The maximum patients are constipated (60%), had mandagni (80%), vata-kapha prakriti (48.33%), rajasika prakriti (58.33%), madhyama vyayama shakti (73.33%), and madhyama jarana shakti (85.83%). Collectively, 43.33% patients were above normal BMI. The more patients had anushna (38.33%) and vishamasana dietary pattern (25.83%), consumed Lavana (88.33%) and Amla rasa (78.33%) in excess on regular basis. Some patients had addicted to tobacco (11.67%) and beetle chewing (5.83%). The maximum patients had no any exercise (79.17%) and specific hobby (79.17%) in their leisure times. Analyzing Hamilton Anxiety and Depression Rating Scales revealed that 39.80%, 37.86%, 33.98%, 24.27% and 18.44% patients had insomnia, depression, tension, GIT symptoms and anxious mood respectively. These data suggest that certain social, dietary and lifestyle factors contribute towards accelerated ageing among young individuals. PMID:22529643

  19. Effect of dietary, social, and lifestyle determinants of accelerated aging and its common clinical presentation: A survey study.

    PubMed

    Samarakoon, S M S; Chandola, H M; Ravishankar, B

    2011-07-01

    Aging is unavoidable and natural phenomenon of life. Modern gerontologists are realizing the fact that aging is a disease, which Ayurveda had accepted as natural disease since long. Rate of aging is determined by one's biological, social, lifestyle, and psychological conditions and adversity of which leads to accelerated form of aging (Akalaja jara or premature aging). The aim of this study is to identify potential factors that may accelerate aging in the context of dietry factors, lifestyle and mental makeup. The 120 diagnosed subjects of premature-ageing of 30-60 years were randomly selected in the survey study. Premature ageing was common among females (75.83%), in 30-40 age group (70%), 86.67% were married, had secondary level of education (36.66%), house-views (61.67%), belongs top middle class (58.33%) and engaged in occupations that dominating physical labour (88.33%). The maximum patients are constipated (60%), had mandagni (80%), vata-kapha prakriti (48.33%), rajasika prakriti (58.33%), madhyama vyayama shakti (73.33%), and madhyama jarana shakti (85.83%). Collectively, 43.33% patients were above normal BMI. The more patients had anushna (38.33%) and vishamasana dietary pattern (25.83%), consumed Lavana (88.33%) and Amla rasa (78.33%) in excess on regular basis. Some patients had addicted to tobacco (11.67%) and beetle chewing (5.83%). The maximum patients had no any exercise (79.17%) and specific hobby (79.17%) in their leisure times. Analyzing Hamilton Anxiety and Depression Rating Scales revealed that 39.80%, 37.86%, 33.98%, 24.27% and 18.44% patients had insomnia, depression, tension, GIT symptoms and anxious mood respectively. These data suggest that certain social, dietary and lifestyle factors contribute towards accelerated ageing among young individuals.

  20. Diffusional anisotropy of the human brain assessed with diffusion-weighted MR: Relation with normal brain development and aging

    SciTech Connect

    Nomura, Toshiyuki; Sakuma, Hajime; Takeda, Kan; Tagami, Tomoyasu; Okuda, Yasuyuki; Nakagawa, Tsuyoshi )

    1994-02-01

    To analyze diffusional anisotropy in frontal and occipital white matter of human brain quantitatively as a function of age by using diffusion-weighted MR imaging. Ten neonates (<1 month), 13 infants (1-10 months), 9 children (1-11 years), and 16 adults (20-79 years) were examined. After taking axial spin-echo images of the brain, diffusion-sensitive gradients were added parallel or perpendicular to the orientation of nerve fibers. The apparent diffusion coefficient parallel to the nerve fibers (0) and that perpendicular to the fibers (90) were computed. The anisotropic ratio (90/0) was calculated as a function of age. Anisotropic ratios of frontal white matter were significantly larger in neonates as compared with infants, children, or adults. The ratios showed rapid decrease until 6 months and thereafter were identical in all subjects. In the occipital lobe, the ratios were also greater in neonates, but the differences from other age groups were not so prominent as in the frontal lobe. Comparing anisotropic ratios between frontal and occipital lobes, a significant difference was observed only in neonates. Diffusion-weighted images demonstrated that the myelination process starts earlier in the occipital lobe than in the frontal lobe. The changes of diffusional anisotropy in white matter are completed within 6 months after birth. Diffusion-weighted imaging provides earlier detection of brain myelination compared with the conventional T1- and T2-weighted images. 18 refs., 6 figs., 1 tab.

  1. Don't Lose Your Brain at Work - The Role of Recurrent Novelty at Work in Cognitive and Brain Aging.

    PubMed

    Oltmanns, Jan; Godde, Ben; Winneke, Axel H; Richter, Götz; Niemann, Claudia; Voelcker-Rehage, Claudia; Schömann, Klaus; Staudinger, Ursula M

    2017-01-01

    Cognitive and brain aging is strongly influenced by everyday settings such as work demands. Long-term exposure to low job complexity, for instance, has detrimental effects on cognitive functioning and regional gray matter (GM) volume. Brain and cognition, however, are also characterized by plasticity. We postulate that the experience of novelty (at work) is one important trigger of plasticity. We investigated the cumulative effect of recurrent exposure to work-task changes (WTC) at low levels of job complexity on GM volume and cognitive functioning of middle-aged production workers across a time window of 17 years. In a case-control study, we found that amount of WTC was associated with better processing speed and working memory as well as with more GM volume in brain regions that have been associated with learning and that show pronounced age-related decline. Recurrent novelty at work may serve as an 'in vivo' intervention that helps counteracting debilitating long-term effects of low job complexity.

  2. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease.

    PubMed

    Klosinski, Lauren P; Yao, Jia; Yin, Fei; Fonteh, Alfred N; Harrington, Michael G; Christensen, Trace A; Trushina, Eugenia; Brinton, Roberta Diaz

    2015-12-01

    White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical.

  3. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease

    PubMed Central

    Klosinski, Lauren P.; Yao, Jia; Yin, Fei; Fonteh, Alfred N.; Harrington, Michael G.; Christensen, Trace A.; Trushina, Eugenia; Brinton, Roberta Diaz

    2015-01-01

    White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical. PMID:26844268

  4. Fluid intelligence and brain functional organization in aging yoga and meditation practitioners

    PubMed Central

    Gard, Tim; Taquet, Maxime; Dixit, Rohan; Hölzel, Britta K.; de Montjoye, Yves-Alexandre; Brach, Narayan; Salat, David H.; Dickerson, Bradford C.; Gray, Jeremy R.; Lazar, Sara W.

    2014-01-01

    Numerous studies have documented the normal age-related decline of neural structure, function, and cognitive performance. Preliminary evidence suggests that meditation may reduce decline in specific cognitive domains and in brain structure. Here we extended this research by investigating the relation between age and fluid intelligence and resting state brain functional network architecture using graph theory, in middle-aged yoga and meditation practitioners, and matched controls. Fluid intelligence declined slower in yoga practitioners and meditators combined than in controls. Resting state functional networks of yoga practitioners and meditators combined were more integrated and more resilient to damage than those of controls. Furthermore, mindfulness was positively correlated with fluid intelligence, resilience, and global network efficiency. These findings reveal the possibility to increase resilience and to slow the decline of fluid intelligence and brain functional architecture and suggest that mindfulness plays a mechanistic role in this preservation. PMID:24795629

  5. Fluid intelligence and brain functional organization in aging yoga and meditation practitioners.

    PubMed

    Gard, Tim; Taquet, Maxime; Dixit, Rohan; Hölzel, Britta K; de Montjoye, Yves-Alexandre; Brach, Narayan; Salat, David H; Dickerson, Bradford C; Gray, Jeremy R; Lazar, Sara W

    2014-01-01

    Numerous studies have documented the normal age-related decline of neural structure, function, and cognitive performance. Preliminary evidence suggests that meditation may reduce decline in specific cognitive domains and in brain structure. Here we extended this research by investigating the relation between age and fluid intelligence and resting state brain functional network architecture using graph theory, in middle-aged yoga and meditation practitioners, and matched controls. Fluid intelligence declined slower in yoga practitioners and meditators combined than in controls. Resting state functional networks of yoga practitioners and meditators combined were more integrated and more resilient to damage than those of controls. Furthermore, mindfulness was positively correlated with fluid intelligence, resilience, and global network efficiency. These findings reveal the possibility to increase resilience and to slow the decline of fluid intelligence and brain functional architecture and suggest that mindfulness plays a mechanistic role in this preservation.

  6. Age-related changes of metallothionein 1/2 and metallothionein 3 expression in rat brain.

    PubMed

    Scudiero, Rosaria; Cigliano, Luisa; Verderame, Mariailaria

    2017-01-01

    Neurodegeneration is one of the main physiological consequences of aging on brain. Metallothioneins (MTs), low molecular weight, cysteine-rich proteins that bind heavy-metal ions and oxygen-free radicals, are commonly expressed in various tissues of mammals. MTs are involved in the regulation of cell proliferation and protection, and may be engaged in aging. Expression of the ubiquitous MTs (1 and 2) and the brain specific MT3 have been studied in many neurodegenerative disorders. The research results indicate that MTs may play important, although not yet fully known, roles in brain diseases; in addition, data lack the ability to identify the MT isoforms functionally involved. The aim of this study was to analyse the level of gene expression of selected MT isoforms during brain aging. By using real-time PCR analysis, we determined the MT1/2 and MT3 expression profiles in cerebral cortex and hippocampus of adolescent (2months), adult (4 and 8months), and middle-aged (16months) rats. We show that the relative abundance of all types of MT transcripts changes during aging in both hippocampus and cortex; the first effect is a generalized decrease in the content of MTs transcripts from 2- to 8-months-old rats. After passing middle age, at 16months, we observe a huge increase in MT3 transcripts in both cortical and hippocampal areas, while the MT1/2 mRNA content increases slightly, returning to the levels measured in adolescent rats. These findings demonstrate an age-related expression of the MT3 gene. A possible link between the increasing amount of MT3 in brain aging and its different metal-binding behaviour is discussed.

  7. Edited Magnetic Resonance Spectroscopy Detects an Age-Related Decline in Nonhuman Primate Brain GABA Levels

    PubMed Central

    Killiany, Ronald J.

    2016-01-01

    Recent research had shown a correlation between aging and decreasing Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain. However, how GABA level varies with age in the medial portion of the brain has not yet been studied. The purpose of this study was to investigate the GABA level variation with age focusing on the posterior cingulate cortex, which is the “core hub” of the default mode network. In this study, 14 monkeys between 4 and 21 years were recruited, and MEGA-PRESS MRS was performed to measure GABA levels, in order to explore a potential link between aging and GABA. Our results showed that a correlation between age and GABA+/Creatine ratio was at the edge of significance (r = −0.523, p = 0.081). There was also a near-significant trend between gray matter/white matter ratio and the GABA+/Creatine ratio (r = −0.518, p = 0.0848). Meanwhile, the correlation between age and grey matter showed no significance (r = −0.028, p = 0.93). Therefore, age and gray matter/white matter ratio account for different part of R-squared (adjusted R-squared = 0.5187) as independent variables for predicting GABA levels. Adjusted R-squared is about 0.5 for two independent variables. These findings suggest that there is internal neurochemical variation of GABA levels in the nonhuman primates associated with normal aging and structural brain decline. PMID:27660760

  8. Effects of polyphenols on brain ageing and Alzheimer's disease: focus on mitochondria.

    PubMed

    Schaffer, Sebastian; Asseburg, Heike; Kuntz, Sabine; Muller, Walter E; Eckert, Gunter P

    2012-08-01

    The global trend of the phenomenon of population ageing has dramatic consequences on public health and the incidence of neurodegenerative diseases. Physiological changes that occur during normal ageing of the brain may exacerbate and initiate pathological processes that may lead to neurodegenerative disorders, especially Alzheimer's disease (AD). Hence, the risk of AD rises exponentially with age. While there is no cure currently available, sufficient intake of certain micronutrients and secondary plant metabolites may prevent disease onset. Polyphenols are highly abundant in the human diet, and several experimental and epidemiological evidences indicate that these secondary plant products have beneficial effects on AD risks. This study reviews current knowledge on the potential of polyphenols and selected polyphenol-rich diets on memory and cognition in human subjects, focusing on recent data showing in vivo efficacy of polyphenols in preventing neurodegenerative events during brain ageing and in dementia. Concentrations of polyphenols in animal brains following oral administration have been consistently reported to be very low, thus eliciting controversial discussion on their neuroprotective effects and potential mechanisms. Whether polyphenols exert any direct antioxidant effects in the brain or rather act by evoking alterations in regulatory systems of the brain or even the body periphery is still unclear. To understand the mechanisms behind the protective abilities of polyphenol-rich foods, an overall understanding of the biotransformation of polyphenols and identification of the various metabolites arising in the human body is also urgently needed.

  9. Assessment of ganglioside age-related and topographic specificity in human brain by Orbitrap mass spectrometry.

    PubMed

    Sarbu, Mirela; Dehelean, Liana; Munteanu, Cristian V A; Vukelić, Željka; Zamfir, Alina D

    2017-03-15

    The gangliosides (GGs) of the central nervous system (CNS) exhibit age and topographic specificity and these patterns may correlate with the functions and pathologies of the brain regions. Here, chloroform extraction, nanoelectrospray (nanoESI) negative ionization, together with Orbitrap high resolution mass spectrometry (MS) determined the topographic and age-related GG specificity in normal adult human brain. Mapping of GG mixtures extracted from 20 to 82 year old frontal and occipital lobes revealed besides a decrease in the GG number with age, a variability of sialylation degree within the brain regions. From the 111 species identified, 105 were distinguished in the FL20, 74 in OL20, 46 in FL82 and 56 in OL82. The results emphasize that within the juvenile brain, GG species exhibit a higher expression in the FL than in OL, while in the aged brain the number of GG species is higher in the OL. By applying MS/MS analysis, the generated fragment ions confirmed the incidence of GT1c (d18:1/18:0) and GT1c (d18:1/20:0) in the investigated samples. The present findings are of major value for further clinical studies carried out using Orbitrap MS in order to correlate gangliosides with CNS disorders.

  10. Regional and Gender Study of Neuronal Density in Brain during Aging and in Alzheimer's Disease

    PubMed Central

    Martínez-Pinilla, Eva; Ordóñez, Cristina; del Valle, Eva; Navarro, Ana; Tolivia, Jorge

    2016-01-01

    Background: Learning processes or language development are only some of the cognitive functions that differ qualitatively between men and women. Gender differences in the brain structure seem to be behind these variations. Indeed, this sexual dimorphism at neuroanatomical level is accompanied unequivocally by differences in the way that aging and neurodegenerative diseases affect men and women brains. Objective: The aim of this study is the analysis of neuronal density in four areas of the hippocampus, and entorhinal and frontal cortices to analyze the possible gender influence during normal aging and in Alzheimer's disease (AD). Methods: Human brain tissues of different age and from both sexes, without neurological pathology and with different Braak's stages of AD, were studied. Neuronal density was quantified using the optical dissector. Results: Our results showed the absence of a significant neuronal loss during aging in non-pathological brains in both sexes. However, we have demonstrated specific punctual significant variations in neuronal density related with the age and gender in some regions of these brains. In fact, we observed a higher neuronal density in CA3 and CA4 hippocampal areas of non-pathological brains of young men compared to women. During AD, we observed a negative correlation between Braak's stages and neuronal density in hippocampus, specifically in CA1 for women and CA3 for men, and in frontal cortex for both, men and women. Conclusion: Our data demonstrated a sexual dimorphism in the neuronal vulnerability to degeneration suggesting the need to consider the gender of the individuals in future studies, regarding neuronal loss in aging and AD, in order to avoid problems in interpreting data. PMID:27679571

  11. Antioxidants, free radicals, storage proteins, puroindolines, and proteolytic activities in bread wheat (Triticum aestivum) seeds during accelerated aging.

    PubMed

    Calucci, Lucia; Capocchi, Antonella; Galleschi, Luciano; Ghiringhelli, Silvia; Pinzino, Calogero; Saviozzi, Franco; Zandomeneghi, Maurizio

    2004-06-30

    Seeds of bread wheat were incubated at 40 degrees C and 100% relative humidity for 0, 3, 4, 6, and 10 days. The effects of accelerated aging on seed germinability and some biochemical properties of flour (carotenoid, free radical, and protein contents and proteolytic activity) and gluten (free radical content and flexibility) were investigated. Seed germinability decreased during aging, resulting in seed death after 10 days. A progressive decrease of carotenoid content, in particular, lutein, was observed, prolonging the incubation, whereas the free radical content increased in both flour and gluten. A degradation of soluble and storage proteins was found, associated with a marked increase of proteolytic activity and a loss of viscoelastic properties of gluten. On the contrary, puroindolines were quite resistant to the treatment. The results are discussed in comparison with those previously obtained during accelerated aging of durum wheat seeds.

  12. White matter hyperintensities and imaging patterns of brain ageing in the general population.

    PubMed

    Habes, Mohamad; Erus, Guray; Toledo, Jon B; Zhang, Tianhao; Bryan, Nick; Launer, Lenore J; Rosseel, Yves; Janowitz, Deborah; Doshi, Jimit; Van der Auwera, Sandra; von Sarnowski, Bettina; Hegenscheid, Katrin; Hosten, Norbert; Homuth, Georg; Völzke, Henry; Schminke, Ulf; Hoffmann, Wolfgang; Grabe, Hans J; Davatzikos, Christos

    2016-04-01

    White matter hyperintensities are associated with increased risk of dementia and cognitive decline. The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer's disease in a large populatison-based sample (n = 2367) encompassing a wide age range (20-90 years), from the Study of Health in Pomerania. We quantified white matter hyperintensities using automated segmentation and summarized atrophy patterns using machine learning methods resulting in two indices: the SPARE-BA index (capturing age-related brain atrophy), and the SPARE-AD index (previously developed to capture patterns of atrophy found in patients with Alzheimer's disease). A characteristic pattern of age-related accumulation of white matter hyperintensities in both periventricular and deep white matter areas was found. Individuals with high white matter hyperintensities burden showed significantly (P < 0.0001) lower SPARE-BA and higher SPARE-AD values compared to those with low white matter hyperintensities burden, indicating that the former had more patterns of atrophy in brain regions typically affected by ageing and Alzheimer's disease dementia. To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant (P < 0.0001) causal relationship between them. Structural equation modelling showed that the age effect on SPARE-BA was mediated by white matter hyperintensities and cardiovascular risk score each explaining 10.4% and 21.6% of the variance, respectively. The direct age effect explained 70.2% of the SPARE-BA variance. Only white matter hyperintensities significantly mediated the age effect on SPARE-AD explaining 32.8% of the variance. The direct age effect explained 66.0% of the SPARE

  13. Accelerated pericyte degeneration and blood–brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer’s disease

    PubMed Central

    Halliday, Matthew R; Rege, Sanket V; Ma, Qingyi; Zhao, Zhen; Miller, Carol A; Winkler, Ethan A

    2016-01-01

    The blood–brain barrier (BBB) limits the entry of neurotoxic blood-derived products and cells into the brain that is required for normal neuronal functioning and information processing. Pericytes maintain the integrity of the BBB and degenerate in Alzheimer’s disease (AD). The BBB is damaged in AD, particularly in individuals carrying apolipoprotein E4 (APOE4) gene, which is a major genetic risk factor for late-onset AD. The mechanisms underlying the BBB breakdown in AD remain, however, elusive. Here, we show accelerated pericyte degeneration in AD APOE4 carriers >AD APOE3 carriers >non-AD controls, which correlates with the magnitude of BBB breakdown to immunoglobulin G and fibrin. We also show accumulation of the proinflammatory cytokine cyclophilin A (CypA) and matrix metalloproteinase-9 (MMP-9) in pericytes and endothelial cells in AD (APOE4 >APOE3), previously shown to lead to BBB breakdown in transgenic APOE4 mice. The levels of the apoE lipoprotein receptor, low-density lipoprotein receptor-related protein-1 (LRP1), were similarly reduced in AD APOE4 and APOE3 carriers. Our data suggest that APOE4 leads to accelerated pericyte loss and enhanced activation of LRP1-dependent CypA–MMP-9 BBB-degrading pathway in pericytes and endothelial cells, which can mediate a greater BBB damage in AD APOE4 compared with AD APOE3 carriers. PMID:25757756

  14. [Research of anti-aging mechanism of ginsenoside Rg1 on brain].

    PubMed

    Li, Cheng-peng; Zhang, Meng-si; Liu, Jun; Geng, Shan; Li, Jing; Zhu, Jia-hong; Zhang, Yan-yan; Jia, Yan-yan; Wang, Lu; Wang, Shun-he; Wang, Ya-ping

    2014-11-01

    Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain, but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain, forty male SD rats were randomly divided into normal group, Rg1 normal group, brain aging model group and Rg1 brain aging model group, each group with 10 rats (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)), qd for 42 consecutive days; Rg1 brain aging model group: while copying the same test as that of brain aging model group, begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group: subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal: injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections). Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD, contents of GSH in hippo- campus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay, respectively. It is pointed that, in brain aging model group, the spatial learning and memory capacities were weaken, SA-beta-Gal positive granules increased in section of brain tissue, the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6 increased in hippocampus, while the length of telomere and the activity of telomerase decreased in hippocampus

  15. Mindfulness and the aging brain: a proposed paradigm shift

    PubMed Central

    Prakash, Ruchika Shaurya; De Leon, Angeline A.; Patterson, Beth; Schirda, Brittney L.; Janssen, Alisha L.

    2014-01-01

    There has been a proliferation of cognitive training studies investigating the efficacy of various cognitive training paradigms as well as strategies for improving cognitive control in the elderly. While some have found support for the transfer of training, the majority of training studies show modest to no transfer effects. When transfer effects have been observed, the mechanisms contributing to enhanced functioning have been difficult to dissociate. In this review, we provide a theoretical rationale for the study of mindfulness in older adults as a particular type of training program designed to improve cognitive control by capitalizing on older adults’ acquired behavioral orientation toward higher socioemotional goals. Given the synergistic relationship between emotional and cognitive control processes, the paradoxical divergence in older adults’ functional trajectory in these respective domains, and the harmonious interplay of cognitive and emotional control embedded in the practice of mindfulness, we propose mindfulness training as an opportunistic approach to cultivating cognitive benefits in older adults. The study of mindfulness within aging, we argue, capitalizes on a fundamental finding of the socioemotional aging literature, namely the preferential change in motivational goals of older adults from ones involving future-oriented wants and desires to present-focused emotion regulation and gratification. PMID:25009492

  16. Age- and diabetes-induced regulation of oxidative protein modification in rat brain and peripheral tissues: consequences of treatment with antioxidant pyridoindole.

    PubMed

    Sakul, Arzu; Cumaoğlu, Ahmet; Aydin, Elif; Ari, Nuray; Dilsiz, Nihat; Karasu, Cimen

    2013-05-01

    The increased glyco- and lipo-oxidation events are considered one of the major factors in the accumulation of non-functional damaged proteins, and the antioxidants may inhibit extensive protein modification and nitrosylated protein levels, enhancing the oxidative damage at the cellular levels in aging and diabetes. Because of its central role in the pathogenesis of age-dependent and diabetes-mediated functional decline, we compared the levels of oxidatively modified protein markers, namely AGEs (Advanced Glycation End-protein adducts), 4-HNE (4-hydroxy-nonenal-histidine) and 3-NT (3-nitrotyrosine), in different tissues of young and old rats. Separately, these three oxidative stress parameters were explored in old rats subjected to experimentally induced diabetes and following a long-term treatment with a novel synthetic pyridoindole antioxidant derived from stobadine-SMe1EC2 (2-ethoxycarbonyl-8-methoxy-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indolinium dichloride). Diabetes induced by streptozotocin injection in rats aged 13-15 months, and SMe1EC2 treatment was applied during 4months to aged diabetic rats. AGEs and 4-HNE levels were significantly elevated in brain, ventricle and kidney, but not in lens and liver of aged rats when compared with young rats. Diabetes propagated ageing-induced increase in AGEs and 4-HNE in brain, ventricle and kidney, and raised significantly lens and liver AGEs and 4-HNE levels in aged rats. In aged diabetic rats, SMe1EC2 protected only the kidney against increase in AGEs, and inhibited significantly 4-HNE levels in brain, kidney, liver and lens that were observed more pronounced in lens. 3-NT was significantly increased in brain of aged rats and in kidney, lens and ventricle of aged diabetic rats, while SMe1EC2 has no protective effect on 3-NT increase. Results demonstrate that (1) the responsiveness of different tissue proteins to glyco-lipo-oxidative and nitrosative stress in the course of normal aging was miscellaneous. (2

  17. Span, CRUNCH, and Beyond: Working Memory Capacity and the Aging Brain

    PubMed Central

    Schneider-Garces, Nils J.; Gordon, Brian A.; Brumback-Peltz, Carrie R.; Shin, Eunsam; Lee, Yukyung; Sutton, Bradley P.; Maclin, Edward L.; Gratton, Gabriele; Fabiani, Monica

    2010-01-01

    Neuroimaging data emphasize that older adults often show greater extent of brain activation than younger adults for similar objective levels of difficulty. A possible interpretation of this finding is that older adults need to recruit neuronal resources at lower loads than younger adults, leaving no resources for higher loads, and thus leading to performance decrements [Compensation-Related Utilization of Neural Circuits Hypothesis; e.g., Reuter-Lorenz, P. A., & Cappell, K. A. Neurocognitive aging and the compensation hypothesis. Current Directions in Psychological Science, 17, 177–182, 2008]. The Compensation-Related Utilization of Neural Circuits Hypothesis leads to the prediction that activation differences between younger and older adults should disappear when task difficulty is made subjectively comparable. In a Sternberg memory search task, this can be achieved by assessing brain activity as a function of load relative to the individual’s memory span, which declines with age. Specifically, we hypothesized a nonlinear relationship between load and both performance and brain activity and predicted that asymptotes in the brain activation function should correlate with performance asymptotes (corresponding to working memory span). The results suggest that age differences in brain activation can be largely attributed to individual variations in working memory span. Interestingly, the brain activation data show a sigmoid relationship with load. Results are discussed in terms of Cowan’s [Cowan, N. The magical number 4 in short-term memory: A reconsideration of mental storage capacity. Behavioral and Brain Sciences, 24, 87–114, 2001] model of working memory and theories of impaired inhibitory processes in aging. PMID:19320550

  18. Exposure to omega-3 fatty acids at early age accelerate bone growth and improve bone quality.

    PubMed

    Koren, Netta; Simsa-Maziel, Stav; Shahar, Ron; Schwartz, Betty; Monsonego-Ornan, Efrat

    2014-06-01

    Omega-3 fatty acids (FAs) are essential nutritional components that must be obtained from foods. Increasing evidence validate that omega-3 FAs are beneficial for bone health, and several mechanisms have been suggested to mediate their effects on bone, including alterations in calcium absorption and urinary calcium loss, prostaglandin synthesis, lipid oxidation, osteoblast formation and inhibition of osteoclastogenesis. However, to date, there is scant information regarding the effect of omega-3 FAs on the developing skeleton during the rapid growth phase. In this study we aim to evaluate the effect of exposure to high levels of omega-3 FAs on bone development and quality during prenatal and early postnatal period. For this purpose, we used the fat-1 transgenic mice that have the ability to convert omega-6 to omega-3 fatty acids and the ATDC5 chondrogenic cell line as models. We show that exposure to high concentrations of omega-3 FAs at a young age accelerates bone growth through alterations of the growth plate, associated with increased chondrocyte proliferation and differentiation. We further propose that those effects are mediated by the receptors G-protein coupled receptor 120 (GPR120) and hepatic nuclear factor 4α, which are expressed by chondrocytes in culture. Additionally, using a combined study on the structural and mechanical bone parameters, we show that high omega-3 levels contribute to superior trabecular and cortical structure, as well as to stiffer bones and improved bone quality. Most interestingly, the fat-1 model allowed us to demonstrate the role of maternal high omega-3 concentration on bone growth during the gestation and postnatal period.

  19. Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss.

    PubMed

    Turner, Russell T; Dube, Michael; Branscum, Adam J; Wong, Carmen P; Olson, Dawn A; Zhong, Xiaoying; Kweh, Mercedes F; Larkin, Iske V; Wronski, Thomas J; Rosen, Clifford J; Kalra, Satya P; Iwaniec, Urszula T

    2015-12-01

    Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin, n=7) or a control vector encoding green fluorescent protein (rAAV-GFP, n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (-4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (-80%), serum leptin (-77%), and serum IGF1 (-34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (P<0.1) in rAAV-GFP-treated rats (13.5 months old) compared to baseline control rats (9 months old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.

  20. Brain aging and its modifiers: insights from in vivo neuromorphometry and susceptibility weighted imaging.

    PubMed

    Raz, Naftali; Rodrigue, Karen M; Haacke, E Mark

    2007-02-01

    Aging is marked by individual differences and differential vulnerability of cognitive operations and their neural substrates. Cross-sectional studies of brain volume reveal greater age-related shrinkage of the prefrontal cortex (PFC) and the hippocampus than in the entorhinal and primary visual cortex. Longitudinal studies of regional brain shrinkage indicate that when individual differences are controlled, larger and broader shrinkage estimates are evident, with most polymodal cortices affected to the same extent. The mechanisms of age-related shrinkage are unclear. Vascular risk factors may exacerbate brain aging and account for some of the observed declines as both the PFC and the hippocampus show elevated vulnerability to hypertension. MRI techniques that are sensitive to small vessels function, tissue oxygenation, and perfusion may be especially well suited to study brain aging and its vascular modifiers. We present an example of one such technique, susceptibility weighted imaging (SWI), that allows direct measurement of T2* values that reflect deoxy- to oxyhemoglobin fraction in blood vessels and iron deposits in cerebral tissue. The T2* shortening is associated with advanced age, but the effect is significantly stronger in the PFC and the hippocampus than the entorhinal and visual cortices. Moreover, T2* is shorter in hypertensive participants than in their matched normotensive counterparts, and the difference is especially prominent in the hippocampus, thus mirroring the findings of the neuromorphometric studies. Future research on brain aging would benefit from combining structural and metabolic techniques in a longitudinal design, as such studies will allow examination of leading-trailing effects of those factors.

  1. Brain tissue volumes in the general population of the elderly: the AGES-Reykjavik study.

    PubMed

    Sigurdsson, Sigurdur; Aspelund, Thor; Forsberg, Lars; Fredriksson, Jesper; Kjartansson, Olafur; Oskarsdottir, Bryndis; Jonsson, Palmi V; Eiriksdottir, Gudny; Harris, Tamara B; Zijdenbos, Alex; van Buchem, Mark A; Launer, Lenore J; Gudnason, Vilmundur

    2012-02-15

    Imaging studies have reported conflicting findings on how brain structure differs with age and sex. This may be explained by discrepancies and limitations in study population and study design. We report a study on brain tissue volumes in one of the largest cohorts of individuals studied to date of subjects with high mean age (mean ± standard deviation (SD) 76 ± 6 years). These analyses are based on magnetic resonance imaging (MRI) scans acquired at baseline on 4303 non-demented elderly, and 367 who had a second MRI, on average 2.5 ± 0.2 years later. Tissue segmentation was performed with an automatic image analysis pipeline. Total brain parenchymal (TBP) volume decreased with increasing age while there was an increase in white matter hyperintensities (WMH) in both sexes. A reduction in both normal white matter (NWM)- and gray matter (GM) volume contributed to the brain shrinkage. After adjusting for intra-cranial volume, women had larger brain volumes compared to men (3.32%, p < 0.001) for TBP volume in the cross-sectional analysis. The longitudinal analysis showed a significant age-sex interaction in TBP volume with a greater rate of annual change in men (-0.70%, 95%CI: -0.78% to -0.63%) than women (-0.55%, 95%CI: -0.61% to -0.49%). The annual change in the cross-sectional data was approximately 40% less than the annual change in the longitudinal data and did not show significant age-sex interaction. The findings indicate that the cross-sectional data underestimate the rate of change in tissue volumes with age as the longitudinal data show greater rate of change in tissue volumes with age for all tissues.

  2. Effects of non-pharmacological or pharmacological interventions on cognition and brain plasticity of aging individuals

    PubMed Central

    Pieramico, Valentina; Esposito, Roberto; Cesinaro, Stefano; Frazzini, Valerio; Sensi, Stefano L.

    2014-01-01

    Brain aging and aging-related neurodegenerative disorders are major health challenges faced by modern societies. Brain aging is associated with cognitive and functional decline and represents the favourable background for the onset and development of dementia. Brain aging is associated with early and subtle anatomo-functional physiological changes that often precede the appearance of clinical signs of cognitive decline. Neuroimaging approaches unveiled the functional correlates of these alterations and helped in the identification of therapeutic targets that can be potentially useful in counteracting age-dependent cognitive decline. A growing body of evidence supports the notion that cognitive stimulation and aerobic training can preserve and enhance operational skills in elderly individuals as well as reduce the incidence of dementia. This review aims at providing an extensive and critical overview of the most recent data that support the efficacy of non-pharmacological and pharmacological interventions aimed at enhancing cognition and brain plasticity in healthy elderly individuals as well as delaying the cognitive decline associated with dementia. PMID:25228860

  3. EEG Resting-State Brain Topological Reorganization as a Function of Age.

    PubMed

    Petti, Manuela; Toppi, Jlenia; Babiloni, Fabio; Cincotti, Febo; Mattia, Donatella; Astolfi, Laura

    2016-01-01

    Resting state connectivity has been increasingly studied to investigate the effects of aging on the brain. A reduced organization in the communication between brain areas was demonstrated by combining a variety of different imaging technologies (fMRI, EEG, and MEG) and graph theory. In this paper, we propose a methodology to get new insights into resting state connectivity and its variations with age, by combining advanced techniques of effective connectivity estimation, graph theoretical approach, and classification by SVM method. We analyzed high density EEG signals recorded at rest from 71 healthy subjects (age: 20-63 years). Weighted and directed connectivity was computed by means of Partial Directed Coherence based on a General Linear Kalman filter approach. To keep the information collected by the estimator, weighted and directed graph indices were extracted from the resulting networks. A relation between brain network properties and age of the subject was found, indicating a tendency of the network to randomly organize increasing with age. This result is also confirmed dividing the whole population into two subgroups according to the age (young and middle-aged adults): significant differences exist in terms of network organization measures. Classification of the subjects by means of such indices returns an accuracy greater than 80%.

  4. Brain levels of sex steroid hormones in men and women during normal aging and in Alzheimer’s disease

    PubMed Central

    Rosario, Emily R.; Chang, Lilly; Head, Elizabeth H.; Stanczyk, Frank Z.; Pike, Christian J.

    2009-01-01

    We examined the relationships between normal aging, Alzheimer’s disease (AD), and brain levels of sex steroid hormones in men and women. In postmortem brain tissue from neuropathologically normal, postmenopausal women, we found no age-related changes in brain levels of either androgens or estrogens. In comparing women with and without AD at different ages, brain levels of estrogens and androgens were lower in AD cases aged 80 years and older but not significantly different in the 60–79 year age range. In male brains, we observed that normal aging was associated with significant decreases in androgens but not estrogens. Further, in men aged 60–79 years, brain levels of testosterone but not estrogens were lower in cases with mild neuropathological changes as well as those with advanced AD neuropathology. In male cases over age 80, brain levels hormones did not significantly vary by neuropathological status. To begin investigating the relationships between hormone levels and indices of AD neuropathology, we measured brain levels of soluble β-amyloid (Aβ). In male cases with mild neuropathological changes, we found an inverse relationship between brain levels of testosterone and soluble Aβ. Collectively, these findings demonstrate sex-specific relationships between normal, age-related depletion of androgens and estrogens in men and women, which may be relevant to development of AD. PMID:19428144

  5. Age and Sex Related Differences in Subcortical Brain Iron Concentrations among Healthy Adults

    PubMed Central

    Persson, Ninni; Wu, Jianlin; Zhang, Qing; Liu, Ting; Shen, Jing; Bao, Ruyi; Ni, Mingfei; Liu, Tian; Wang, Yi; Spincemaille, Pascal

    2015-01-01

    Age and sex can influence brain iron levels. We studied the influence of these variables on deep gray matter magnetic susceptibilities. In 183 healthy volunteers (44.7 ± 14.2 years, range 20-69, ♀ 49%), in vivo Quantitative Susceptibility Mapping (QSM) at 1.5T was performed to estimate brain iron accumulation in the following regions of interest (ROIs): caudate nucleus (Cd), putamen (Pt), globus pallidus (Gp), thalamus (Th), pulvinar (Pul), red nucleus (Rn), substantia nigra (Sn) and the cerebellar dentate nuclei (Dn). We gauged the influence of age and sex on magnetic susceptibility by specifying a series of Structural Equation Models. The distributions of susceptibility varied in degree across the structures, conforming to histologic findings (Hallgren & Sourander, 1958), with the highest degree of susceptibility in the Gp and the lowest in the Th. Iron increase correlated across several ROIs, which may reflect an underlying age-related process. Advanced age was associated with a particularly strong linear rise of susceptibility in the striatum. Nonlinear age trends were found in the Rn, where they were the most pronounced, followed by the Pul and Sn, while minimal nonlinear trends were observed for the Pt, Th, and Dn. Moreover, sex related variations were observed, so that women showed lower levels of susceptibility in the Sn after accounting for age. Regional susceptibility of the Pul increased linearly with age in men but exhibited a nonlinear association with age in women with a leveling off starting from midlife. Women expected to be post menopause (+51 years) showed lower total magnetic susceptibility in the subcortical gray matter. The current report is consistent with previous reports of age related variations of brain iron, but also adds to the current knowledge by reporting age-related changes in less studied, smaller subcortical nuclei. This is the first in-vivo report to show lower total subcortical brain iron levels selectively in women from

  6. Differential expression of sirtuin family members in the developing, adult, and aged rat brain.

    PubMed

    Sidorova-Darmos, Elena; Wither, Robert G; Shulyakova, Natalya; Fisher, Carl; Ratnam, Melanie; Aarts, Michelle; Lilge, Lothar; Monnier, Philippe P; Eubanks, James H

    2014-01-01

    The sirtuins are NAD(+)-dependent protein deacetylases and/or ADP-ribosyltransferases that play roles in metabolic homeostasis, stress response and potentially aging. This enzyme family resides in different subcellular compartments, and acts on a number of different targets in the nucleus, cytoplasm and in the mitochondria. Despite their recognized ability to regulate metabolic processes, the roles played by specific sirtuins in the brain-the most energy demanding tissue in the body-remains less well investigated and understood. In the present study, we examined the regional mRNA and protein expression patterns of individual sirtuin family members in the developing, adult, and aged rat brain. Our results show that while each sirtuin is expressed in the brain at each of these different stages, they display unique spatial and temporal expression patterns within the brain. Further, for specific members of the family, the protein expression profile did not coincide with their respective mRNA expression profile. Moreover, using primary cultures enriched for neurons and astrocytes respectively, we found that specific sirtuin members display preferential neural lineage expression. Collectively, these results provide the first composite illustration that sirtuin family members display differential expression patterns in the brain, and provide evidence that specific sirtuins could potentially be targeted to achieve cell-type selective effects within the brain.

  7. Impact of Markov Random Field Optimizer on MRI-based Tissue Segmentation in the Aging Brain

    PubMed Central

    Schwarz, Christopher G.; Tsui, Alex; Fletcher, Evan; Singh, Baljeet; DeCarli, Charles; Carmichael, Owen

    2013-01-01

    Automatically segmenting brain magnetic resonance images into grey matter, white matter, and cerebrospinal fluid compartments is a fundamentally important neuroimaging problem whose difficulty is heightened in the presence of aging and neurodegenerative disease. Current methods overlap greatly in terms of identifiable algorithmic components, and the impact of specific components on performance is generally unclear in important real-world scenarios involving serial scanning, multiple scanners, and neurodegenerative disease. Therefore we evaluated the impact that one such component, the Markov Random Field (MRF) optimizer that encourages spatially-smooth tissue labelings, has on brain tissue segmentation performance. Two challenging elderly sets were used to test segmentation consistency across scanners and biological plausibility of tissue change estimates; and a simulated young brain data set was used to test accuracy against ground truth. Comparisons among Graph Cuts (GC), Belief Propagation (BP), and Iterative Conditional Modes (ICM) suggested that in the elderly brain, BP and GC provide the highest segmentation performance, with a slight advantage to BP, and that performance is often superior to that provided by popular methods SPM and FAST. Conversely, SPM and FAST excelled in the young brain, thus emphasizing the unique challenges involved in imaging the aging brain. PMID:22256150

  8. The increase of the functional entropy of the human brain with age.

    PubMed

    Yao, Y; Lu, W L; Xu, B; Li, C B; Lin, C P; Waxman, D; Feng, J F

    2013-10-09

    We use entropy to characterize intrinsic ageing properties of the human brain. Analysis of fMRI data from a large dataset of individuals, using resting state BOLD signals, demonstrated that a functional entropy associated with brain activity increases with age. During an average lifespan, the entropy, which was calculated from a population of individuals, increased by approximately 0.1 bits, due to correlations in BOLD activity becoming more widely distributed. We attribute this to the number of excitatory neurons and the excitatory conductance decreasing with age. Incorporating these properties into a computational model leads to quantitatively similar results to the fMRI data. Our dataset involved males and females and we found significant differences between them. The entropy of males at birth was lower than that of females. However, the entropies of the two sexes increase at different rates, and intersect at approximately 50 years; after this age, males have a larger entropy.

  9. Cytidine diphosphate choline administration activates brain cytidine triphosphate: phosphocholine cytidylytransferase in aged rats.

    PubMed

    Giménez, R; Soler, S; Aguilar, J

    1999-10-08

    Beneficial effects of cytidine (5') diphosphocholine (CDP-choline) administration on several diseases including brain aging, ischemia and stroke are based on an increase in membrane phospholipid turnover. We have studied the possible involvement of CTP:phosphocholine cytidylyltransferase (CT) in this mechanism by measuring its gene expression and enzyme activity in the brains of young and aged rats treated with 500 mg/kg per day of CDP-choline. Older animals showed higher (57%) of total CT activity in particulate (active) fraction than younger animals (46%). Treatment of aged animals for 8, 16, or 60 days had no effect on the CT gene expression but increased activation of the CT by translocation to membranes. The particulate fraction rose from 57% of total activity to more than 65% after 2 months of treatment. This may explain the long-term repairing effects of CDP-choline on damaged membranes of aged animals.

  10. A culture-brain link: Negative age stereotypes predict Alzheimer's disease biomarkers.

    PubMed

    Levy, Becca R; Ferrucci, Luigi; Zonderman, Alan B; Slade, Martin D; Troncoso, Juan; Resnick, Susan M

    2016-02-01

    Although negative age stereotypes have been found to predict adverse outcomes among older individuals, it was unknown whether the influence of stereotypes extends to brain changes associated with Alzheimer's disease. To consider this possibility, we drew on dementia-free participants, in the Baltimore Longitudinal Study of Aging, whose age stereotypes were assessed decades before yearly magnetic resonance images and brain autopsies were performed. Those holding more-negative age stereotypes earlier in life had significantly steeper hippocampal-volume loss and significantly greater accumulation of neurofibrillary tangles and amyloid plaques, adjusting for relevant covariates. These findings suggest a new pathway to identifying mechanisms and potential interventions related to the pathology of Alzheimer's disease.

  11. Taurine content in different brain structures during ageing: effect on hippocampal synaptic plasticity.

    PubMed

    Suárez, Luz M; Muñoz, María-Dolores; Martín Del Río, Rafael; Solís, José M

    2016-05-01

    A reduction in taurine content accompanies the ageing process in many tissues. In fact, the decline of brain taurine levels has been associated with cognitive deficits whereas chronic administration of taurine seems to ameliorate age-related deficits such as memory acquisition and retention. In the present study, using rats of three age groups (young, adult and aged) we determined whether the content of taurine and other amino acids (glutamate, serine, glutamine, glycine, alanine and GABA) was altered during ageing in different brain areas (cerebellum, cortex and hippocampus) as well non-brain tissues (heart, kidney, liver and plasma). Moreover, using hippocampal slices we tested whether ageing affects synaptic function and plasticity. These parameters were also determined in aged rats fed with either taurine-devoid or taurine-supplemented diets. With age, we found heterogeneous changes in amino acid content depending on the amino acid type and the tissue. In the case of taurine, its content was reduced in the cerebellum of adult and aged rats, but it remained unchanged in the hippocampus, cortex, heart and liver. The synaptic response amplitude decreased in aged rats, although the late phase of long-term synaptic potentiation (late-LTP), a taurine-dependent process, was not altered. Our study highlights the stability of taurine content in the hippocampus during ageing regardless of whether taurine was present in the diet, which is consistent with the lack of changes detected in late-LTP. These results indicate that the beneficial effects of taurine supplementation might be independent of the replenishment of taurine stores.

  12. Dose-Volume Response Relationship for Brain Metastases Treated with Frameless Single-Fraction Linear Accelerator-Based Stereotactic Radiosurgery

    PubMed Central

    Pan, Jianmin; Yusuf, Mehran B; Dragun, Anthony; Dunlap, Neal; Guan, Timothy; Boling, Warren; Rai, Shesh; Woo, Shiao

    2016-01-01

    Background: Our aim was to identify a dose-volume response relationship for brain metastases treated with frameless stereotactic radiosurgery (SRS). Methods: We reviewed patients who underwent frameless single-fraction linear accelerator SRS for brain metastases between 2007 and 2013 from an institutional database. Proportional hazards modeling was used to identify predictors of outcome. A ratio of maximum lesion dose per mm-diameter (Gy/mm) was constructed to establish a dose-volume relationship. Results: There were 316 metastases evaluated in 121 patients (2 - 33 mm in the largest diameter). The median peripheral dose was 18.0 Gy (range: 10.0 – 24.0 Gy). Local control was 84.8% for all lesions and was affected by location, peripheral dose, maximum dose, and lesion size (p values < 0.050). A dose-volume response relationship was constructed using the maximum dose and lesion size. A unit increase in Gy/mm was associated with decreased local failure (p = 0.005). Local control of 80%, 85%, and 90% corresponded to maximum doses per millimeter of 1.67 Gy/mm, 2.86 Gy/mm, and 4.4 Gy/mm, respectively. Toxicity was uncommon and only 1.0% of lesions developed radionecrosis requiring surgery. Conclusions: For brain metastases less than 3 cm, a dose-volume response relationship exists between maximum radiosurgical dose and lesion size, which is predictive of local control. PMID:27284495

  13. Identification of Cerebral Metal Ion Imbalance in the Brain of Aging Octodon degus

    PubMed Central

    Braidy, Nady; Poljak, Anne; Marjo, Chris; Rutlidge, Helen; Rich, Anne; Jugder, Bat-Erdene; Jayasena, Tharusha; Inestrosa, Nibaldo C.; Sachdev, Perminder S.

    2017-01-01

    The accumulation of redox-active transition metals in the brain and metal dyshomeostasis are thought to be associated with the etiology and pathogenesis of several neurodegenerative diseases, and Alzheimer’s disease (AD) in particular. As well, distinct biometal imaging and role of metal uptake transporters are central to understanding AD pathogenesis and aging but remain elusive, due inappropriate detection methods. We therefore hypothesized that Octodon degus develop neuropathological abnormalities in the distribution of redox active biometals, and this effect may be due to alterations in the expression of lysosomal protein, major Fe/Cu transporters, and selected Zn transporters (ZnTs and ZIPs). Herein, we report the distribution profile of biometals in the aged brain of the endemic Chilean rodent O. degus—a natural model to investigate the role of metals on the onset and progression of AD. Using laser ablation inductively coupled plasma mass spectrometry, our quantitative images of biometals (Fe, Ca, Zn, Cu, and Al) appear significantly elevated in the aged O. degus and show an age-dependent rise. The metals Fe, Ca, Zn, and Cu were specifically enriched in the cortex and hippocampus, which are the regions where amyloid plaques, tau phosphorylation and glial alterations are most commonly reported, whilst Al was enriched in the hippocampus alone. Using whole brain extracts, age-related deregulation of metal trafficking pathways was also observed in O. degus. More specifically, we observed impaired lysosomal function, demonstrated by increased cathepsin D protein expression. An age-related reduction in the expression of subunit B2 of V-ATPase, and significant increases in amyloid beta peptide 42 (Aβ42), and the metal transporter ATP13a2 were also observed. Although the protein expression levels of the zinc transporters, ZnT (1,3,4,6, and 7), and ZIP7,8 and ZIP14 increased in the brain of aged O. degus, ZnT10, decreased. Although no significant age

  14. Effect of high-intensity exercise on aged mouse brain mitochondria, neurogenesis, and inflammation.

    PubMed

    E, Lezi; Burns, Jeffrey M; Swerdlow, Russell H

    2014-11-01

    In aged mice, we assessed how intensive exercise affects brain bioenergetics, inflammation, and neurogenesis-relevant parameters. After 8 weeks of a supra-lactate threshold treadmill exercise intervention, 21-month-old C57BL/6 mice showed increased brain peroxisome proliferator-activated receptor gamma coactivator-1α protein, mammalian target of rapamycin and phospho-mammalian target of rapamycin protein, citrate synthase messenger RNA, and mitochondrial DNA copy number. Hippocampal vascular endothelial growth factor A (VEGF-A) gene expression trended higher, and a positive correlation between VEGF-A and PRC messenger RNA levels was observed. Brain doublecortin, brain-derived neurotrophic factor, tumor necrosis factor-α, and CCL11 gene expression, as well as plasma CCL11 protein levels, were unchanged. Despite these apparent negative findings, a negative correlation between plasma CCL11 protein levels and hippocampal doublecortin gene expression was observed; further analysis indicated exercise may mitigate this relationship. Overall, our data suggest supra-lactate threshold exercise activates a partial mitochondrial biogenesis in aged mice, and a gene (VEGF-A) known to support neurogenesis. Our data are consistent with another study that found systemic inflammation in general, and CCL11 protein specifically, suppresses hippocampal neurogenesis. Our study supports the view that intense exercise above the lactate threshold may benefit the aging brain; future studies to address the extent to which exercise-generated lactate mediates the observed effects are warranted.